摘要:

Background Cardiac transplantation and chronic myocardial infarction interrupt vagal afferent nerve fibers, which originate mainly from the ventricles. Marked abnormalities of reflexes mediated by cardiopulmonary receptors with vagal afferent fibers have been demonstrated after both cardiac transplantation and chronic myocardial infarction. The relation between these reflex abnormalities and ventricular deafferentation is not known.Methods and Results To further assess this relation, we investigated the effects of left ventricular (LV) deafferentation on the control of renal sympathetic nerve activity (RSNA) by the vagal cardiopulmonary reflex in chloralose-anesthetized, mechanically ventilated dogs with sinoaortic denervation. Responses of left atrial pressure (LAP) and RSNA to hemorrhage and volume expansion were measured before and after application of 88% phenol to either the inferoposterior LV (n=12) or the entire LV (n=14). In control experiments, measurements were made before and after application of saline to the LV (n=12). Reflex sensitivity (percent change in RSNA per mm Hg change in LAP) measured during volume expansion was mildly attenuated after both total (prephenol, -9.1+-0.7; postphenol, -6.6+-0.7; P<.05) and inferoposterior (pre, -12.5+-1.8; post, -8.1+-0.6; P=.055) LV deafferentation. Reflex sensitivity measured during hemorrhage was not significantly altered by inferoposterior or total LV deafferentation. Epicardial saline had no significant effect on reflex sensitivity values measured during either volume expansion or hemorrhage. Reflex inhibition of RSNA in response to intracoronary nicotine was abolished after phenol application, indicating adequate ventricular deafferentation. Phenol application had no significant effect on LAP-myocardial segment length relations measured by sonomicrometry (n=6).Conclusions Interruption of vagal afferent input from the LV has only modest effects on the control of RSNA by the vagal cardiopulmonary reflex. These data indicate that there is considerable redundancy in the vagal cardiopulmonary reflex such that receptors from the lungs and other cardiac chambers can largely compensate for the loss of afferent input from the LV. (Circulation. 1994;90:2015-2021.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Stretch-induced arrhythmias (SIAs) can be elicited in normal canine left ventricles by transient diastolic dilatation. Since clinically important ventricular arrhythmias arise most commonly in failing and dilated ventricles, we hypothesized that the arrhythmogenic effect of transient diastolic stretch would be enhanced in chronically dilated failing canine hearts.Methods and Results Heart failure was induced in seven dogs by right ventricular pacing at 250 min sup -1 for 20.2+-1.6 days. Left ventricular (LV) mechanical properties were measured in vivo with serial echocardiograms in these seven dogs with the dogs awake and tranquilized to confirm the development of LV dilation and failure. By the third week of pacing, average short-axis area ejection fraction decreased by 64.3% (P<.001) as end-diastolic and end-systolic diameters increased by 25.9% and 50.7%, respectively (P<.001). After heart failure was established, the hearts were harvested and in vitro data were obtained as an isolated, blood-perfused ventricle preparation. A computerized servo pump system connected to an LV intracavitary balloon was used to measure and control LV volume. Results were compared with in vitro data obtained from eight ventricles not subjected to pacing (controls). LV contractility, quantitated in vitro as the slope of the peak isovolumic pressure-volume relation (Emax) normalized to LV cavity size, was much lower in the heart failure group than in controls (182+-18 versus 365+-38 mm Hg, P<.001). In all isolated hearts, SIAs were induced using an electromechanical stimulation protocol in which eight paced beats at 2 Hz were followed by a transient increase in LV volume during early diastole. Prestretch volume (Vi) was selected to yield end-diastolic pressures of 4 to 8 mm Hg in all hearts. The fractional increase in LV volume (Delta V) that produced SIAs 50% of the time (Delta V sub 50/Vi) was smaller in failing hearts than in controls (0.78+-0.04 versus 1.18+-0.17, P=.009), indicating an increased sensitivity to SIAs in the failing hearts. Although ventricular pairs were occasionally induced in both groups, the great majority of the arrhythmias induced in both groups were single extrasystoles, and nonsustained runs of ventricular tachycardia were never elicited in either group. LV end-diastolic and peak stretch pressures were similar in the two groups, but LV end-diastolic wall stress was higher by 35.7% (P=.029) in the dilated failing ventricles because LV hypertrophy, which tends to normalize wall stress as the heart dilates, did not occur during the 3 weeks of pacing. For stretch stimuli of comparable arrhythmogenic effectiveness, peak LV wall stress during stretch was similar in the two groups, whereas the fractional increase in volume was significantly smaller in the heart failure group, indicating impaired viscoelastic properties in the failing ventricles. In five control ventricles, acute exposure to 0.5 micromole/L dobutamine increased ventricular sensitivity to the induction of SIAs, as shown by a decrease in Delta V50/Vifrom 1.27+-0.16 to 1.06+-0.11 (P=.04).Conclusions Altered mechanical properties and/or neurohumoral adaptations associated with chronic dilation and failure predispose the ventricle to induction of ventricular extrasystoles by transient LV diastolic stretch. (Circulation. 1994;90:2022-2031.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Drug therapy to maintain sinus rhythm in patients with atrial fibrillation (AF) is limited by adverse effects and inadequate efficacy. There has been an increased interest in the use of class III drugs to treat AF, and several new agents have been developed, but there is little information available about mechanisms of class III drug action in AF. The present study was designed to compare the effects of two class III agents, d-sotalol and ambasilide, in dog models of experimental AF.Methods and Results A previously developed dog model of sustained vagotonic AF was used to assess the ability of equal loading doses of d-sotalol and ambasilide (2 mg/kg, followed by maintenance infusions), to terminate AF and prevent its induction. At this dose, ambasilide terminated AF in 12 of 12 dogs and prevented AF induction in 10 of 12 dogs; d-sotalol terminated AF in 1 of 8 dogs (P=.001 versus ambasilide) and prevented AF induction in none of 8 dogs (P=.002). An additional dose of d-sotalol (cumulative load, 8 mg/kg) terminated AF in 7 of 8 dogs and prevented induction in 5 of 8 dogs. In an additional 6 dogs with sterile pericarditis and inducible AF, ambasilide prevented AF induction in all 6. An equal dose of d-sotalol (2 mg/kg) failed to suppress AF induction in any dog, but 8 mg/kg of d-sotalol suppressed AF induction in all. Atrial effective refractory period (AERP) was increased by both drugs. However, the effects of d-sotalol on AERP showed strong reverse use dependence, whereas those of ambasilide did not. Neither ambasilide nor d-sotalol significantly altered conduction velocity, and both increased ventricular refractoriness, with d-sotalol once again showing more reverse use dependence. Effective doses of both agents increased AERP and the wavelength for atrial reentry at rapid rates, slowing atrial activation and terminating the arrhythmia.Conclusions The class III drugs d-sotalol and ambasilide terminate AF by increasing AERP and the wavelength for reentry. Ambasilide, which has been reported to block both the rapid and slow components of the delayed rectifier (IKrand IKs), shows less reverse use dependence of effects on refractoriness than the pure IKrblocker d-sotalol, possibly explaining the greater effectiveness of ambasilide at an equal dose level. These results indicate that class III drugs can exhibit different profiles of rate-dependent action on AERP and suggest that it may be possible to develop agents that have more desirable rate-dependent profiles than pure blockers of Ikr. (Circulation. 1994;90:2032-2040.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Left atrial pressure (LAP) is often believed to play a dominant role in the determination of left ventricular (LV) early diastolic filling. In a previous study we found no significant relation between LAP and LV early filling velocity (E) but found instead a relation between E and two determinants of LV myocardial shortening (contractility and afterload). To determine if such disparate results may be related to the data ranges of the independent variables in a given population of animals, we took advantage of the differential hemodynamic effects of two modes of volume expansion: saline and whole blood.Methods and Results Eighteen closed-chest anesthetized dogs were instrumented with micromanometers for measurement of LV, left atrial, and aortic pressures. LV volumes were obtained with use of contrast ventriculography, pressures by micromanometry, and transmitral flow-velocity by Doppler echocardiography. After obtaining baseline measurements, group 1 (n=9) received rapid infusion of 500 to 650 mL of saline over 10 minutes, and group 2 (n=9) received the same volume infusion of whole blood. In terms of two known determinants of E, infusion of saline resulted in a significant increase in LAP at the moment of mitral valve opening (X1) (1.5+-0.9 to 5.7+-1.4 mm Hg; P<.05) and a moderate decrease in the pressure decay rate during isovolumic relaxation (tau1/2) (22.9+-2.4 to 26.3+-3.5 milliseconds; P<.05). When these two factors were entered together into a multiple regression analysis with E as the dependent variable, the overall correlation was found to be significant (R=.722; P<.008), with both independent variables contributing significantly to the relation. When factors related to myocardial shortening (afterload and contractility) were added to this relation, they did not significantly improve the prediction of E. Like saline, whole blood infusion augmented X1(1.6+-2.4 to 8.8+-3.2 mm Hg; P<.05) and tau1/2 (21.5+-2.6 to 32.0+-6.3 milliseconds; P<.05) but also significantly increased LV afterload as measured by aortic diastolic pressure (91+-10 to 110+-12 mm Hg; P<.05). Multiple regression analysis of X1and tau1/2 with E again revealed a significant relation (R=.761; P<.002), with both independent variables contributing significantly to the relation. However, in this case, addition of contractility and afterload to the regression significantly improved the relation (R=.909; P<.001), with all four independent variables now contributing significantly to the prediction of E.Conclusions Combined with our previous results, this study indicates the degree to which experimental methods can have an impact on the delineation of the determinants of a phenomenon as complex as LV early diastolic filling. Which independent variables emerge as primary determinants can be strongly influenced by the experimenter's choice of experimental design and manipulations. Specifically, experiments using volume infusion to delineate the responses of the cardiovascular system to variations in loading must allow for the hemodynamic changes that are inherent in the choice of infusate and infusion technique, especially when those interventions may significantly alter blood oxygen-carrying capacity and, in turn, differentially modify factors that affect the magnitude of the early diastolic transmitral pressure gradient. (Circulation. 1994;90:2041-2050.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Recently, an angiotensin-converting enzyme inhibitor was shown to have a beneficial effect on virus-induced myocardial injury. We investigated the effect of a new angiotensin II type 1 receptor antagonist, (+-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-((2'-(1H-tetrazol- 5-yl)biphenyl-4-yl)methyl)-1H-benzimidazole-7-carboxylate (TCV-116), in an animal model of viral myocarditis induced by encephalomyocarditis virus.Methods and Results Four-week-old DBA/2 mice were inoculated with the encephalomyocarditis virus. TCV-116 (in 5% gum arabic) was given 1 day before (1 or 10 mg/kg) or 2 days after virus inoculation (0.3 or 3 mg/kg). Control mice received the vehicle only. All drugs were administered orally on a daily basis, and the animals were killed on day 14. When treatment was started 1 day before inoculation, the survival of mice receiving 10 mg/kg of TCV-116 improved (17 of 20 (85%) versus 14 of 22 (64%) control mice), but the difference was not significant. Heart weight (106+-24 mg versus 133+-33 mg, P<.05), histological scores for myocardial necrosis (1.1+-0.3 versus 2.3+-1.2, P<.01), cellular infiltration (1.4+-0.7 versus 2.6+-1.3, P<.05), and calcification (1.1+-0.3 versus 2.1+-1.1, P<.01) were significantly decreased in mice given TCV-116 at 3 mg/kg compared with the vehicle control mice. The plasma angiotensin II level was significantly higher in infected mice than in noninfected mice (71.8+-30.2 versus 31.8+-22.5 pg/mL, P<.05). TCV-116 did not inhibit viral replication in the heart.Conclusions This study suggests that angiotensin II plays an important pathophysiological role in viral myocarditis. Treatment with TCV-116, an angiotensin II receptor antagonist, had a cardioprotective effect. (Circulation. 1994;90:2051-2055.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Multiple clinical trials have provided guidelines for the treatment of myocardial infarction, but there is little documentation as to how consistently their recommendations are being implemented in clinical practice.Methods and Results Demographic, procedural, and outcome data from patients with acute myocardial infarction were collected at 1073 US hospitals collaborating in the National Registry of Myocardial Infarction during 1990 through 1993. Registry hospitals composed 14.4% of all US hospitals and were more likely to have a coronary care unit and invasive cardiac facilities than nonregistry US hospitals. Among 240 989 patients with myocardial infarction enrolled, 84 477 (35.1%) received thrombolytic therapy. Thrombolytic recipients were younger, more likely to be male, presented sooner after onset of symptoms, and were more likely to have localizing ECG changes. Among the 60 430 patients treated with recombinant tissue-type plasminogen activator (rTPA), 23.2% received it in the coronary care unit rather than in the emergency department. Elapsed time from hospital presentation to starting rTPA averaged 99 minutes (median, 57 minutes). Among patients receiving thrombolytic therapy, concomitant pharmacotherapy included intravenous heparin (96.9%), aspirin (84.0%), intravenous nitroglycerin (76.0%), oral beta -blockers (36.3%), calcium channel blockers (29.5%), and intravenous beta -blockers (17.4%). Invasive procedures in thrombolytic recipients included coronary arteriography (70.7%), angioplasty (30.3%), and bypass surgery (13.3%). Trend analyses from 1990 to 1993 suggest that the time from hospital evaluation to initiating thrombolytic therapy is shortening, usage of aspirin and beta -blockers is increasing, and usage of calcium channel blockers is decreasing.Conclusions This large registry experience suggests that management of myocardial infarction in the United States does not yet conform to many of the recent clinical trial recommendations. Thrombolytic therapy is underused, particularly in the elderly and late presenters. Although emerging trends toward more appropriate treatment are evident, hospital delay time in initiating thrombolytic therapy remains long, aspirin and beta -blockers appear to be underused, and calcium channel blockers and invasive procedures appear to be overused. (Circulation. 1994;90:2103-2114.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID