摘要:

BackgroundAttenuation of myocardial stunning by several angiotensin-converting enzyme (ACE) inhibitors has been demonstrated. However, the signal cascade mediating such protective effect has not been analyzed in detail so far.Methods and ResultsIn a first protocol, we addressed the role of bradykinin and analyzed the effect of the ACE inhibitor ramiprilat without and with added bradykinin B2receptor antagonist HOE 140 on regional myocardial blood flow (colored microspheres) and function (sonomicrometry). Thirtytwo enflurane/N2O-anesthetized open-chest dogs were subjected to 15 minutes of occlusion of the left circumflex coronary artery (LCx) and 4 hours of subsequent reperfusion. Eight dogs served as placebo controls (group 1), and 8 dogs received ramiprilat (20 μg/kg IV) before LCx occlusion (group 2). Eight dogs received a continuous intracoronary infusion of HOE 140 [0.5 ng/(mL · min) IC] during ischemia and reperfusion (group 3), and in 8 dogs HOE 140 was infused continuously during ischemia and reperfusion, starting 45 minutes before the administration of ramiprilat (group 4). Mean aortic pressure was kept constant with an intra-aortic balloon, and heart rate did not change throughout the experimental protocols. Under control conditions and during myocardial ischemia, posterior transmural blood flow (BF) and systolic wall thickening (WT) were not different in the four groups of dogs. However, at 4 hours of reperfusion, WT was still depressed in groups 1 (− 10±20% of control [mean±SD]), 3 (−18±12% of control), and 4 (−12±21% of control), whereas WT in group 2 had recovered to 55 ±20% of control (P<.05 versus group 1). BF at 4 hours of reperfusion was not different in the four groups of dogs. Thus, the beneficial effect of ramiprilat on the functional recovery of stunned myocardium was obviously mediated by bradykinin. Since bradykinin stimulates the formation of both prostaglandins and nitric oxide, we tested in a second protocol which of these mediators was further involved in the beneficial effects of ramiprilat. Twenty-four additional dogs were subjected to 15 minutes of LCx occlusion and 4 hours of reperfusion. Six dogs received the cyclooxygenase inhibitor indomethacin (10 mg/kg IV) (group 5) and 6 dogs a combination of indomethacin with ramiprilat (group 6) before LCx occlusion. Six dogs received the nitric oxide synthase inhibitorNG-nitro-L-arginine methyl ester (L-NAME) (20 mg/kg IV) (group 7) and 6 dogs a combination of L-NAME with ramiprilat (group 8) before LCx occlusion. BF and WT before and during myocardial ischemia were not different in groups 5 and 6 and groups 7 and 8. However, at 4 hours of reperfusion, WT was still depressed in groups 5 (−10±38% of control), 6 (−7±18% of control), and 7 (−12±14% of control), whereas WT in group 8 had recovered to 47±28% of control (P<.05 versus group 7). BF at 4 hours of reperfusion was not different in the four groups of dogs.ConclusionsIn summary, the attenuation of stunning by the ACE inhibitor ramiprilat involves a signal cascade of bradykinin and prostaglandins but not nitric oxide.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundIn patients with ventricular dysfunction caused by stunning or hibernation, it is not clear when complete recovery of the salvaged myocardium occurs after acute myocardial infarction. The purpose of this study was to determine whether a delayed recovery of perfusion and contraction continues even after the subacute phase.Methods and ResultsWe prospectively studied 71 consecutive male patients with first uncomplicated Q-wave anterior infarction. Resting regional blood flow distribution and contraction were assessed quantitatively 5 weeks and 7 months after the acute phase by serial sestamibi tomography and two-dimensional echocardiography. Coronary angiography also was performed in 52 patients. Overall, at 7 months there was an improvement in the perfusion defect severity (1019±811 versus 1365±821 at 5 weeks,P<.001) as well as in the extent of abnormal wall motion (28±19% versus 32±15%,P<.001) and left ventricular ejection fraction (53±14% versus 50±13%,P<.01). Among the 68 of 71 patients showing resting perfusion defects at 5 weeks, two groups were identified: 47 (group 1) who showed a significant (beyond the reproducibility limits) 7-month reduction of the resting perfusion defect, and 21 patients (group 2) in whom the perfusion defect remained unchanged. Ejection fraction and the extent of abnormal wall motion significantly (P<.01) improved in group 1 but not in group 2. Despite the presence of a comparable perfusion defect size between the two groups at 5 weeks after infarction, group 1 already showed a better regional and global ventricular function (P<.05). No significant differences were found between the two groups regarding age, medical therapy, the extent of underlying coronary disease, thrombolysis in the acute phase, Thrombolysis in Myocardial Infarction grade of the infarct-related vessel, and presence of collaterals on angiography.ConclusionsAfter anterior Q-wave infarction, the recovery of perfusion and wall motion may continue well after the subacute phase. Several patients exhibit relative hypoperfusion in viable tissue as late as 5 weeks after infarction, and a significant improvement of perfusion in the infarcted area commonly is observed between 5 weeks and 7 months. This delayed improvement of perfusion is associated with a delayed improvement of contractile function in the infarcted area after the first 5 weeks, which may continue for up to 7 months, suggesting the presence of hibemating myocardium in the infarcted area. Despite similar perfusion defect sizes, the level of regional function can be different at 5 weeks, and measurements taken around this time may not accurately estimate the eventual recovery of function.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundRight ventricular free wall (RVFW) ischemia impairs global RV performance and may result in acute hemodynamic compromise. However, RV function and hemodynamic performance typically improve spontaneously over time. This study was designed to determine whether reperfusion facilitates recovery of function in the ischemic right ventricle.Methods and ResultsClosed chest dogs underwent right coronary balloon occlusion for 1 hour (n =9), 4 hours (n =6), or 8 hours (n=7). In all animals, occlusion depressed RVFW function and global RV performance. After 1 hour of ischemia, reperfusion led to immediate improvement in RVFW function and consequently global RV performance, with complete recovery over 4 weeks and scar in <1% of total RVFW area. Reperfusion after 4- and 8-hour occlusions resulted in acute improvement in global RV performance but to a lesser extent and by different mechanisms, since RVFW contraction remained severely impaired. This disproportionate recovery of global RV function was attributable to diminished RVFW dyskinesis associated with reperfusion-induced increments in RVFW diastolic thickness (characterized histopathologically in 6 additional animals subjected to 4-hour occlusions but killed 1 hour after reperfusion by interstitial edema, contraction band necrosis, and hemorrhage). Although later reperfusion was associated with a slower pace and lesser extent of recovery, RVFW contraction improved markedly over time. At 4 weeks, there was trivial RVFW scar in 4-hour animals (2% of total RVFW area), and, although fibrosis was significantly greater in 8-hour animals (7% of RVFW area), infarction was minimal relative to the extent of jeopardized myocardium.ConclusionsThe responses of ischemic RV myocardium to reperfusion are complex, with disparate effects according to the duration of preceding ischemia. Early reperfusion results in prompt improvement in and subsequent complete recovery of RVFW contraction and global RV performance, with trivial or no RVFW scar. Late reperfusion leads to little acute recovery of RVFW function, but global performance improves owing to diminished RVFW dyskinesis associated with reperfusion-induced increments in RVFW diastolic thickness. Nevertheless, RVFW function improves over time, with minimal evidence of infarction. Therefore, reperfusion facilitates recovery of RV function and minimizes the extent of infarction even after prolonged ischemia.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundWe tested the hypotheses that long-term administration of the angiotensin-converting enzyme (ACE) inhibitor fosinopril will regress hypertrophy, modify the transition to heart failure, and prolong survival in rats with chronic left ventricular (LV) pressure overload due to ascending aortic stenosis.Methods and ResultsAortic stenosis was created in weanling male Wistar rats by a stainless steel clip placed on the ascending aorta. Age-matched control animals underwent a sham operation (Sham group, n=57). Six weeks after surgery, rats with aortic stenosis were randomized to receive either oral fosinopril 50 mg · kg−1· d−1(Fos/LVH group, n=38) or no drug (LVH group, n=36) for 15 weeks. Pilot studies confirmed that this dosage produced significant inhibition of LV tissue ACE in vivo. Animals were monitored daily, and survival during the 15-week treatment period was assessed by actuarial analysis. At 15 weeks, in vivo LV systolic and diastolic pressures and heart rate were measured. To assess contractile function, the force-calcium relation was evaluated by use of the isovolumic buffer-perfused, balloon-in-LV heart preparation at comparable coronary flow rates per gram LV weight. Quantitative morphometry was performed. Mortality during the 15-week trial was significantly less in the Fos/LVH group than in the LVH group (3% versus 31%,P<.005). No deaths occurred in the Sham group. In vivo LV systolic pressure was similar between Fos/LVH and LVH hearts (223±10 versus 232±9 mm Hg) and significantly higher than the Sham group (99±3 mm Hg,P<.05). In vivo LV diastolic pressure was significantly lower in Fos/LVH hearts than in LVH hearts (10±2 versus 15±2 mm Hg), and both were significantly higher than in the Sham group (5±1 mm Hg,P<.05). Heart rate was similar among all groups. Despite equivalent elevation of LV systolic pressure, fosinopril resulted in regression of myocyte hypertrophy in Fos/LVH versus LVH (myocyte cell width, 14.8±0.5 versus 20.8±2.2 μm,P<.05) to normal levels (Sham, 16.3±0.9 μm). Quantitative morphometry demonstrated that the regression of LV myocyte hypertrophy in the Fos/LVH group was associated with a relative increase in the fractional volume of fibrillar collagen and noncollagen interstitium. In the isolated heart experiments, LV systolic developed pressure relative to perfusate [Ca2+] was significantly higher in Fos/LVH hearts than in LVH hearts. The improvement in systolic function was not related to any difference in myocardial high-energy phosphate levels, since LV ATP and creatine phosphate levels were similar in Fos/LVH and LVH hearts.ConclusionsIn rats with ascending aortic stenosis, chronic ACE inhibition with fosinopril improved survival, decreased the extent of LV hypertrophy, and improved cardiac function despite persistent elevation of LV systolic pressure. The favorable effects of fosinopril may be related in part to inhibition of the effects of cardiac ACE on myocyte hypertrophy rather than to systemic hemodynamic mechanisms.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundRapid ventricular pacing for 1 day reduced myocardial contractile function without inducing heart failure in conscious, chronically instrumented dogs. After 4 to 7 weeks of pacing, myocardial contractility was depressed further and overt signs of congestive heart failure, eg, ascites, dyspnea, and edema, were evident.Methods and ResultsThe mechanical restitution response, a physiological index of calcium release, was depressed at 1 day of rapid ventricular pacing. Postextrasystolic potentiation was also depressed by a similar amount, 14±3%, at 1 day after pacing. The response to isoproterenol 0.2 μg/kg per minute was depressed by a significantly greater amount (P<.05), 52±7%, at 1 day after pacing.3H-ryanodine receptor binding fell from 1013±25 to 808±42 fmol/mg after 1 day of pacing and remained depressed at similar levels (782±61 fmol/mg) at 4 to 7 weeks when heart failure was manifest. Ryanodine receptor affinity was unchanged from control values. Neither dihydropyridine binding nor affinity for3H-PN200-110 was changed from control levels. Within 5 days after recovery from 1 day of pacing, physiological responses to isoproterenol, postextrasystolic potentiation, and mechanical restitution recovered, as did3H-ryanodine binding density.ConclusionsThese findings suggest that the changes in excitation-contraction coupling and potentially the sarcoplasmic reticulum calcium release channel occur early in the development of heart failure and therefore may be important in the pathogenesis of the contractile abnormalities in this disease state.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundEnd-systolic elastance (Ees), the slope parameter of the end-systolic pressure (ESP)-volume (ESV) relation (ESPVR), is usually estimated in patients by producing stepwise, steady-state pharmacological afterload variations and collecting one ESP-ESV point from each step. The ESPVR is then constructed by fitting a linear equation to these points. In sedated, autonomically blocked dogs, it has been shown that when one point from control, one point from a state of increased afterload, and one point from a state of decreased afterload are used, the resulting Ees, incorrectly estimates true Ees, defined as the slope of the ESPVR obtained by transient vena caval occlusion. We investigated if this was also the case in unsedated, autonomically intact dogs when the points used belonged to steady states of progressively decreasing or progressively increasing afterload pressure.Methods and ResultsIn 10 conscious dogs instrumented with left ventricular (LV) endocardial sonomicrometers to measure LV volume, a LV pressure transducer, and an inferior vena caval (IVC) occluder, two protocols were carried out on separate days. In each protocol, an ESPVR was generated by IVC occlusion in the control state and in two steady-state levels of afterload change produced by stepwise infusion of nitroprusside (protocol 1, afterload decrease) and angiotensin II (protocol 2, afterload increase). In each protocol, steadystate ESP-ESV data points were averaged from the control state and from each level of afterload variation. Linear equations were fitted to the three steady-state points from each protocol, and the estimated Eesvalues obtained (EesEST) were compared with the Eesvalues of the control ESPVRs obtained by IVC occlusion (EesTRUE). In protocol 1, EesEST underestimated EesTRUE by about 16% (EesEST, 6.49±1.55 mm Hg/mL; EesTRUE, 7.48±1.29 mm Hg/mL;P<.02). In protocol 2, BesEST overestimated EesTRUE by about 37% (EesEST, 9.99±3.97 mm Hg/mL; EesTRUE, 6.43±3.88 mm Hg/mL;P<.007).ConclusionsIn conscious, autonomically intact dogs, the use of stepwise, steady-state afterload variations to obtain ESP-ESV data points to construct the ESPVR incorrectly estimates Ees. In the case of afterload reduction, EesTRUE is underestimated an average of 16.3%, and in the case of afterload increase, EesTRUE is overestimated an average of 37.1%. These errors should be taken into account when interpreting clinical studies using this methodology.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe present study was performed to define the mechanisms underlying spontaneously occurring ventricular arrhythmias in the failing heart.Methods and ResultsThree-dimensional cardiac mapping from as many as 232 intramural sites was performed in five dogs with ischemic cardiomyopathy induced by multiple intracoronary embolizations. After 5 to 10 weekly embolizations with 90-μm latex microspheres into the left anterior and circumflex coronary arteries, left ventricular ejection fraction decreased from 63±3% to 22±3%. Subsequent weekly Holter monitoring of dogs in the conscious state demonstrated frequent multiform premature ventricular complexes (PVCs) (≤2000/d), couplets, and runs of ventricular tachycardia (VT) (≤70 beats in duration and ≤560 beats per minute) in all dogs. Three-dimensional mapping of spontaneous rhythm for 60 minutes was performed an average of 6.4 weeks after the last embolization, during which time each dog demonstrated multiform PVCs, couplets, and runs of nonsustained VT at rates comparable to those in the conscious state. Mapping was of sufficient density to define the mechanism for 31 PVCs, 45 beats of ventricular couplets, and 99 beats of VT. Sinus beats preceding PVCs (n=36) initiated in the septum and spread rapidly with a total activation time (46±1 milliseconds) that did not differ from that of sinus beats not preceding PVCs or VT (46±2 milliseconds, n= 10,P=.69). PVCs and the first beat of couplets or VT were initiated primarily in the subendocardium by a focal mechanism, based on the lack of intervening electrical activity between the termination of the preceding (sinus) beat and initiation of the ectopic beat (225±23 milliseconds), despite the presence of multiple intervening intramural recording sites. All subsequent beats of VT also were initiated by a focal mechanism, and their total activation time (89±1 milliseconds) did not differ from that of the initiating ectopic beats (86±2 milliseconds,P=.14), despite acceleration of VT to a cycle length of 200 milliseconds. Monomorphic VT was due to repetitive focal activation of subendocardial sites. Polymorphic VT was due to sequential focal activation from multiple sites arising in the subendocardium and, at times, in the subepicardium. Comparison of mapping data with results of detailed anatomic analysis of tissue demonstrated that focal sites of initiation exhibited patchy nontransmural fibrosis. Functional conduction delay of a moderate degree was evident only when fibrosis extended transmurally.ConclusionsSpontaneously occurring PVCs, couplets, and VT in a model of ischemic cardiomyopathy are initiated and maintained by focal mechanisms with no evidence of macroreentry. Thus, therapeutic regimens to treat or prevent VT in the presence of ischemic cardiomyopathy will likely require interruption of these focal mechanisms.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe functional pathways of efferent sympathetic and vagal innervation to the right ventricle (RV) might be important in a variety of disease states that involve the RV wall. The purpose of this study was to investigate those pathways.Methods and ResultsWe determined the effects of phenol and endocardial radiofrequency ablation applied to the RV anterolateral wall and outflow tract on effective refractory period (ERP) shortening during bilateral ansae subclaviae stimulation and ERP lengthening during bilateral vagal stimulation. We found that efferent sympathetic axons to the RV are located in the superficial subepicardium and that lateral sites receive sympathetic innervation predominantly from the lateral margin of the RV near the AV groove. Medial sites close to the left anterior descending coronary artery (LAD) receive sympathetic innervation from both the right lateral atrioventricular (AV) groove and regions near the LAD. At the RV outflow tract, some sympathetic fibers are located intramurally. Efferent vagal fibers are located at the RV surface within 10 mm of the right lateral AV groove; they penetrate intramurally and reach to the medial sites of the RV anterior wall. Other vagal fibers originate near the LAD and are intramural. Vagal fibers to the RV outflow tract are located intramurally either from the lateral side (close to the right coronary artery) or medial side (close to the LAD).ConclusionsEfferent vagal and sympathetic innervation of the right ventricle resembles that of the left ventricle. A major difference is that efferent sympathetic fibers to the right ventricular outflow tract are located not only in the subepicardium but in the subendocardium as well.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundHeterogeneities of repolarization (R) across the myocardium have been invoked to explain most reentrant arrhythmias. The measurement of refractory periods (RPs) has been widely used to assess R, but conventional electrode and extrastimulus mapping techniques have not provided reliable maps of RPs.Methods and ResultsGuinea pig hearts were stained with a voltage-sensitive dye to measure fluorescence (F) action potentials (APs) from 124 sites with a photodiode array. AP duration (APD) was defined as the time between depolarization (dF/dt)maxand R time points (ie, the time when AP returns to baseline or some percent thereof). However, R time points are difficult to determine because AP downstrokes are often encumbered by drifting baselines and motion artifacts, which make this definition ambiguous. In optical and microelectrode recordings, the second derivative of AP downstrokes is shown to contain an easily detected, unique local maximum. The correlation between the position of this maximum (d2F/dt2)max, and R has been tested during altered AP characteristics induced by changes in cycle length, ischemia, and hypoxia. Under these various modifications of the AP, the time points of (d2F/dt2)maxfell at 97.0±2.1% of recovery to baseline. Extrastimulus techniques applied to (1) isolated myocytes, (2) intact hearts, and (3) mathematical simulations indicated that (d2V/dt2)maxcoincided with the effective RPs of APs. The coincidence of RPs and (d2V/dt2)maxwas valid within 5 milliseconds, for resting potentials of −75 to −90 mV and extrastimuli three times threshold voltage.ConclusionsThus, optical APs and (d2F/dt2)maxcan be used to map activation, R, and RPs with AP recordings from a single heartbeat.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundOur objective was to examine the accuracy of intracardiac ultrasound (ICUS) measurement of left ventricular (LV) volumes and ejection fraction (EF) using a 10-MHz ultrasound catheter. ICUS can image the LV in cross sections at all levels along the long axis with a transducer mounted on the tip of a catheter. Sequential serial LV cross-sectional images can be obtained during cardiac catheterization and used to calculate LV volumes by Simpson's rule. This technique may be an alternative to contrast LV angiography.Methods and ResultsA beating-heart in vivo model was created to measure LV volume directly and continuously with an intracavity high-compliance latex balloon connected to a calibrated extracardiac reservoir in eight dogs in 35 experimental stages. A 1OF ICUS catheter with a 10-MHz single-element transducer was introduced retrogradely via the aortic valve to the apex. Series of sequential LV cross-sectional images were recorded from the apex to the base during a calibrated pullback of the catheter. At each 5-mm interval, the LV cross section was traced at end diastole and end systole. LV volume was calculated by Simpson's rule by integrating all segmental areas multiplied by segmental height. The effect on accuracy of selecting 5-, 10-, or 15-mm heights or a single section at the midventricular level for measurement was assessed. The influence of distorted ventricular shape on the accuracy of ICUS measurements of LV volume was evaluated. This method was applied in 19 experimental stages in 10 intact dogs and pigs catheterized via the femoral artery. In the in vivo canine model, LV end-diastolic volume, end-systolic volume, and EF determined by ICUS using 5-, 10-, or 15-mm segments were not different from the actual measurements. But correlation and agreement between ICUS end-diastolic volume and direct measurements for 5- and 10-mm segments were significantly better than for 15-mm segments or a single section. Similar excellent correlations and agreement were observed for actual and ICUS-derived end-systolic volumes using 5-, 10-, or 15-mm segments. The ICUS-derived EF correlated very well with actual EF with a small measurement error of 3.91±2.59% for 5-mm or 4.13 ±2.79% for 10-mm segments but a significantly greater measurement error for 15-mm segments (5.35±3.76%) or single sections (14.8±12.2%). The presence of LV infarction or aneurysm did not significantly influence the accuracy of ICUS calculations for segmental heights 510 mm. Application in intact animals demonstrated a good correlation between stroke volume measured by ICUS and by thermodilution or flowmeter. ICUS-derived LV volumes correlated well with biplane angiographic volumes, with a tendency toward underestimation. There was no significant difference between ICUS-determined LV EF and EF determined by angiography.ConclusionsIntracardiac echocardiography accurately measures LV volumes and global systolic function in both regularly shaped and distorted left ventricles. This technique directly and continuously visualizes circumferential LV endocardium and wall thickness without contrast agents or geometric assumptions for calculation of LV volume. Thus, it should be particularly useful in patients at high risk for contrast-related complications or distorted LV shapes in which geometric assumptions may not be valid.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID