摘要:

BackgroundWe previously reported a delayed phase of protection against infarction 24 hours after ischemic preconditioning in the rabbit. In the present study, we investigated the possibility that this “second window of protection,” like the well-described early phase of protection in the rabbit, might be associated with adenosine receptor activation.Methods and ResultsIn the first series of experiments, we examined whether adenosine receptor blockade with 8-(p-sulfophenyl)- theophylline (SPT) during preconditioning could abolish the delayed protection against infarction 24 hours later. Open-chest rabbits were subjected to myocardial preconditioning (PC) with the four 5-minute coronary occlusions or they were sham operated on (SHAM). During these procedures, animals received either SPT (PC + SPT, n = 6; and SHAM + SPT, n = 6) or vehicle (PC + VEH, n = 12; and SHAM + VEH, n = 11). Twenty-four hours later, infarct development after a 30-minute coronary occlusion/120-minute reperfusion insult was assessed with triphenyltetrazolium staining. In vehicle-treated rabbits, the infarct-to-risk ratio (I/R) was reduced from 53.6 ± 5.7% (SHAM + VEH) to 32.9 ± 4.6% (PC + VEH) (P< .05), clearly indicating a delayed phase of protection. Although I/R was not significantly different between SHAM + VEH (53.6 ± 5.7%) and SHAM + SPT (61.7 ± 5.4%), in PC + SPT the delayed protection was abolished (I/R = 56.8 ± 3.8%). In the second series of experiments, we examined if pharmacological adenosine A1receptor stimulation could evoke a delayed phase of protection. Conscious rabbits were pretreated with intravenous boluses of saline or the A1receptor–selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA), and infarct size in response to 30-minute ischemia/120-minute reperfusion was assessed 24 hours later. I/R was 54.5 ± 2.7% in saline-pretreated controls (n = 12). Pretreatment with 25 μg/kg CCPA (n = 6), 50 μg/kg CCPA (n = 6), or 100 μg/kg CCPA (n = 6) resulted in I/R ratios of 37.1 ± 4.2% (P< .01), 37.7 ± 2.2% (P< .01), and 26.3 ± 5.7% (P< .01), respectively. In both series of experiments, there were no differences in systemic hemodynamics during the infarct protocol, assessed as rate-pressure product, between the different experimental groups.ConclusionsTwenty-four hours after repetitive brief coronary occlusions, susceptibility to infarction in rabbit myocardium is reduced, an effect that may have clinical relevance. Results of the present study suggest that this second window of protection following preconditioning may, like the early phase of protection, be initiated by an adenosine-related mechanism.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundRestenosis after balloon angioplasty of coronary arteries is thought to be a proliferative response of the arterial wall to injury. Recently, it has been suggested that geometric remodeling of the arterial wall, rather than intimal fibromuscular hyperplasia, may be the major pathophysiological mechanism underlying restenosis. In this study, we evaluated the relative contribution of a geometric decrease in arterial size versus neointimal growth to luminal narrowing associated with restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.Methods and ResultsFocal femoral atherosclerosis was induced by endothelial desiccation injury followed by a 2% cholesterol diet. After 1 month on the high cholesterol diet, the animals were subjected to one of four strategies: (1) balloon angioplasty, (2) balloon angioplasty followed by treatment with the factor Xa inhibitor antistasin, (3) combined laser and balloon angioplasty, or (4) no angioplasty. Animals were killed 2 hours or 28 days after angioplasty, and excised femoral artery segments were prepared for histomorphometric analysis. Angiography was performed serially before and immediately after angioplasty and before the animals were killed. An initial postprocedural gain in luminal diameter at sites of angioplasty was followed by a significant reduction in diameter by angiography and a significant increase in luminal cross-sectional area narrowing by plaque by histomorphometry 28 days after angioplasty compared to adjacent nonangioplastied segments of the same arteries, to nonangioplastied control arteries, or to angioplastied segments of animals treated with the factor Xa inhibitor antistasin. By contrast, the overall arterial size (cross-sectional area bounded by the external elastic lamina) at sites of restenosis was not significantly different from adjacent nonangioplastied segments in the majority of arteries excised at 28 days, and the mean overall arterial size at sites of restenosis was not significantly different from corresponding segments of nonangioplastied control arteries or from angioplastied segments of animals treated with antistasin. In the minority of angioplastied arteries in which the arterial size did change, most got larger.ConclusionsGeometric remodeling resulting in a decrease in overall cross-sectional arterial size does not appear to be the principal pathogenetic mechanism for restenosis after balloon angioplasty with or without laser in this experimental model.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundConduction mediated by the slow inward (Ca2+) current occurs in vitro under specific experimental conditions but has not been documented in ventricular muscle in vivo during regional myocardial ischemia, perhaps because certain constituents of ischemia (including hypoxia and acidosis) may inhibit the Ca2+current in this setting. We hypothesized that slow conduction mediated by the Ca2+current could occur during acute ischemia in situations in which the extracellular K+rise was more marked relative to the degree of acidosis, as may occur at ischemic boundaries.Methods and ResultsIn open-chest, anesthetized swine, an arterial shunt from the carotid artery to the mid-left anterior descending coronary artery was created through which a solution of KCl was infused to raise extracellular K+([K+]e) to approximately 9.4 mmol/L before the initiation of ischemia, which we termed “K+-modified ischemia.” Ischemia initiated at a normal [K+]e(“unmodified ischemia”) resulted in a mean activation delay in the center of the ischemic zone of 55 ± 26 milliseconds after 5 minutes of ischemia and a decrease in epicardial longitudinal conduction velocity from 53 to 21 cm/s before the onset of conduction block. K+- modified ischemia resulted in a mean activation delay in the center of the ischemic zone of 181 ± 8 milliseconds and a decrease in epicardial longitudinal conduction to less than 10 cm/s. K+-modified ischemia was associated with ventricular fibrillation in 85% of episodes compared with 28% of episodes of unmodified ischemia (P< .01). Verapamil prevented the occurrence of marked activation delay during K(+)-modified ischemia, producing local activation block following a maximum activation delay of 74 ± 25 milliseconds. In two experiments, responses mediated by the slow inward current were produced by regional K+elevation to 15 to 16 mmol/L, followed by concomitant regional administration of epinephrine (10−7mol/L). Regional [K+]eelevation alone to this level resulted in local activation block following a maximum activity delay of 70 to 80 milliseconds, whereas administration of epinephrine in combination with high [K+]eresulted in return of local activation with an activation delay of 160 to 180 milliseconds (ie, similar to that during K+- modified ischemia).ConclusionsCompared with unmodified ischemia, K+-modified ischemia resulted in marked activation delay and a high incidence of ventricular fibrillation. Based on measurements of longitudinal conduction velocity, the inhibitory effect of verapamil, and the results of experiments with high [K+]e plus epinephrine, we conclude that the marked activation delay during K+-modified ischemia represents conduction mediated by the slow inward current. Because the conditions produced by K+-modified ischemia (high [K+]e with minimal acidosis) are similar to conditions in and near ischemic border regions, we hypothesize that responses mediated by the slow inward current may occur in such regions during unmodified ischemia and may participate in the development of reentrant arrhythmias.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundCyclosporin A is reported to impair endothelium-mediated vasorelaxation and induce endothelin release in some noncoronary vascular beds. We wished to determine whether acute cyclosporine administration induces endothelial dysfunction in coronary conductance or resistance arteries.Methods and ResultsWe examined the effect of intracoronary acetylcholine, N omega-nitro-L-arginine methyl ester (L- NAME), L-arginine, nitroglycerin, and adenosine before and after acute cyclosporine administration (3 mg/kg IV over 30 minutes) in anesthetized dogs. Flow velocity was measured with a 0.014-in Doppler wire to assess resistance vessel responses, and epicardial coronary lumen area was simultaneously measured with a 4.3F, 30-MHz imaging catheter inserted over the Doppler wire. In 6 dogs, acetylcholine-induced increase in flow velocity was attenuated by cyclosporine in vehicle (137% to 55% at 10−5mol/L,P< .001), as was acetylcholine- induced epicardial vasodilation (14.1% to 6.7% at 10−5mol/L,P< .001). Vasodilation in response to intracoronary nitroglycerin (200 μg) and adenosine (6 mg) were unchanged by cyclosporine. Epicardial vasoconstriction with L-NAME (10−4mol/L) was reduced by cyclosporine (Pre, 7.4 ± 0.9%; Post, 2.6 ± 1.2%;P= .04), but L- arginine (10−4mol/L) had no effect after cyclosporine. In another 5 dogs, pure cyclosporine impaired acetylcholine-induced vasodilatation to the same degree as cyclosporine in vehicle (Cremophor); vehicle infusion did not impair endothelial function. In 5 more dogs, cyclosporine did not increase either arterial or coronary sinus concentrations of endothelin-1.ConclusionsThe present study shows that cyclosporine acutely impairs release of endothelium-derived relaxing factor in canine conductance and resistance coronary arteries and provides evidence for decreased epicardial nitric oxide release after cyclosporine. The potential contribution of acute cyclosporine- induced coronary endothelial dysfunction to posttransplant vasculopathy needs further study.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe effect of genetic hypertension and of chronic therapy by calcium entry blocker (CEB, isradipine) on the function and structure of large arteries has been studied in adult spontaneously hypertensive rats (SHR, n = 30) and in their normotensive control Wistar-Kyoto (WKY) rats (n = 30).Methods and ResultsFifteen-week-old rats were randomly allocated to treatment with isradipine (3 mg/kg subcutaneously once a day) or to placebo and followed for 12 weeks. Hemodynamic parameters, including instantaneous pressure and aortic velocity, were recorded under anesthesia at the end of the treatment period. Passive mechanical properties of carotid arteries were measured in situ in the presence or the absence of smooth muscle cell activity (potassium cyanide poisoning). Histomorphometric parameters of the carotid and aortic media, including cross-sectional area, medial thickness, nucleus density and size, and medial contents of proteins of interstitial matrix, were measured by an automated morphometric system. Untreated SHRs had greater peripheral resistance, stiffer and thicker arterial walls because of smooth muscle cell hyperplasia (thoracic aorta and carotid artery) and/or hypertrophy (thoracic aorta), and increased collagen content than did normotensive control rats. SHRs showed a significant left ventricular hypertrophy. For the whole duration of treatment, treatment with CEB normalized the arterial pressure in SHRs. We observed a significant decrease in peripheral resistance, increased cardiac output, and left ventricular contractility without significant reduction in left ventricular hypertrophy. Increases in diuresis and natriuresis were associated during the last week of treatment in both treated strains with marked increase in plasma renin activity; in contrast, urinary aldosterone was increased by treatment in WKY rats but not in SHRs. Arterial compliance was significantly increased by CEB under control and passive conditions. CEB induced a significant reduction in the medial hypertrophy of the aortic walls of SHRs and WKY rats associated with a reduction in medial hyperplasia. In the carotid artery, CEB reduced smooth muscle cell hypertrophy but did not affect the smooth muscle cell hyperplasia. Isradipine significantly reduced the arterial wall collagen contents in both strains, with marked increases in the elastin content in the carotid but not in the aortic wall.ConclusionsThese results suggest that (1) despite normalization of arterial pressure, chronic treatment with CEB in SHRs does not significantly reduce left ventricular hypertrophy, probably because of increase in myocardial contractility and/or increase in plasma renin activity; (2) mechanical properties of the arterial wall are normalized by treatment; and (3) remodeling of the arterial wall by CEB is not uniform according to the studied vessel.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundProgressive ventricular remodeling after myocardial damage is associated with a poor prognosis. Optimal prevention of the histopathological processes involved in remodeling requires a more complete understanding of the mechanisms involved in initiating and maintaining these structural changes. Since the sympathetic nervous system and the renin-angiotensin system may be involved in the remodeling process, the structural effects of pharmacological inhibitors have been evaluated in a canine model of localized myocardial injury resulting from transmyocardial DC shock.Methods and ResultsThe study is comprised of two protocols run in series. In protocol 1, zofenopril (Z), a converting enzyme inhibitor (CEI), prevented the increase in left ventricular mass (LVM) and end-diastolic volume (LVV) observed in the control group (C) at 16 weeks (Z: LVM, 69.8 ± 3.4 to 65.4 ± 2.6 g,P= NS; LVV, 45.4 ± 2.7 to 51.6 ± 2.7 mL, P = NS; C: LVM, 68.4 ± 3.2 to 91.4 ± 2.9 g,P= .0001; LVV, 56.6 ± 3.0 to 71.9 ± 2.4 mL,P= .0003). Terazosin, an alpha 1- adrenoceptor antagonist, failed to prevent remodeling at 16 weeks despite continued receptor blockade. In protocol 2, the antiremodeling effect of full-dose CEI therapy with ramipril was confirmed. Low-dose ramipril that exerted no hemodynamic effect failed to prevent remodeling (LVM, 89.7 ± 4.6 to 105.7 ± 3.4 g,P= .01; LVV, 61.8 ± 3.8 to 76.8 ± 3.3 mL,P= .002). An angiotensin II subtype 1 receptor blocker also failed to prevent the increase in LVM or LVV (LVM, 89.0 ± 4.6 to 109.7 ± 5.3 g,P= .0001; LVV, 66.0 ± 1.9 to 78.4 ± 3.6 mL,P= .007).ConclusionsHigh-dose CEI therapy can prevent progressive structural changes resulting from localized myocardial damage induced by DC shock. The failure of α1-adrenoceptor blockade and angiotensin II subtype 1 blockade to attenuate remodeling argues against an important direct role for norepinephrine acting through α1-receptors or angiotensin II acting through the type 1 receptor in the remodeling process in this model.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundWe studied the effect of exercise (7.2 to 8.0 km/h) on the efficiency of the conversion of metabolic energy to external work or stroke work (SW) by the left ventricle (LV).Methods and ResultsEnergy use was calculated from LV myocardial oxygen consumption per beat (M&OV0622;O2). LV volume was calculated from orthogonal dimensions and coronary flow measured with ultrasonic flow probes. The total mechanical energy of the LV was calculated as the pressure-volume area (PVA). At rest, the M&OV0622;O2-PVA point fell on the M&OV0622;O2-PVA relation determined by steady-state changes in arterial pressure produced by graded infusions of phenylephrine. Exercise increased the slope (Ees) of LV end-systolic pressure-volume (PV) relation by 29%. During exercise, the M&OV0622;O2-PVA point shifted to the right only slightly above the control M&OV0622;O2-PVA relation by 0.007 ± 0.005 mL O2.beat−1.100 g LV−1. Despite the increase in ventricular contractility with exercise, the PVA/M&OV0622;O2ratio was unchanged because of the marked increase in PVA. During exercise, the transmission of total mechanical energy to external work (SW/PVA) increased from 65 ± 5% to 72 ± 4% (P< .01) as the ratio of the arterial end-systolic elastance to Eesdecreased from 1.1 ± 0.2 to 0.8 ± 0.1 (P< .05). Thus, LV mechanical efficiency (SW/M&OV0622;O2= SW/PVA.PVA/M&OV0622;O2) improved from 12.9 ± 1.5% to 14.3 ± 1.1% (P< .05) during exercise.ConclusionsExercise increases the efficiency of conversion of metabolic energy to external work by the LV due to alteration in LV arterial coupling resulting in increased production of mechanical energy and enhanced transmission of mechanical energy to external work, which more than offsets any increased metabolic cost of the enhanced contractility.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundSystolic shortening is known to produce muscle deactivation. The present study was designed to analyze whether the velocity and the timing of ejection play a role on end-systolic pressure-volume relations (ESPVR).Methods and ResultsIn isolated rabbit hearts, left ventricular pressure and volume were recorded and digitized, and left ventricular volume was controlled by a servosystem (4-millisecond cycles) to alter the timing of ejection. A significant deficit in end-systolic pressure was observed when ejection was late in systole with respect to earlier ejection. This was associated with a significantly reduced end-systolic elastance. End-systolic pressure of beats with slow ejection was intermediate between that of the beats with early ejection and that of beats with late ejection with a significantly increased end-systolic volume compared with beats with early rapid ejection. The same results were obtained with hypertrophied hearts (abdominal aortic stenosis). Pressure-volume loop areas were significantly increased in beats with slow ejections and with rapid delayed ejections versus early rapid ejections. No change in the positive peak of dP/dt was observed when the timing and the velocity of ejection were modified.ConclusionsESPVR is modified by the ejection profile, with a decreased end-systolic pressure and an increased pressure-volume loop area related to the velocity and the amount of shortening during the end-systolic phase. These indices of ventricular function thus must be used with caution when the timing of ejection is altered, and the end-diastolic volume-peak dP/dt relation may be a better index of ventricular function.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundThe need for ventilation during the initial management of cardiac arrest is an important public health problem that is being debated. The present study was designed to determine whether ventilation affects return of spontaneous circulation from cardiac arrest in a swine model with an interval of untreated ventricular fibrillation of 6 minutes, as reported in witnessed out-of-hospital human cardiac arrest.Methods and ResultsTwenty-four animals were randomly assigned to two groups: one that received ventilation during the first 10 minutes of chest compression and one that did not. Coronary perfusion pressure and minute ventilation were continuously recorded. Arterial and mixed venous blood gases were measured at intervals. Return of spontaneous circulation was defined prospectively as an aortic systolic blood pressure of > 80 mm Hg for > 5 minutes and was the primary outcome variable. All animals were anesthetized, paralyzed, and intubated. Ventricular fibrillation was induced and persisted for 6 minutes without chest compression, followed by mechanical chest compression for 10 minutes and then attempted defibrillation. Animals without return of spontaneous circulation were given epinephrine, ventilation, and chest compression for an additional 3 minutes. Defibrillation was again attempted, and animals were assessed for return of spontaneous circulation. There were no significant differences between the two groups in baseline prearrest mean cardiac index, coronary perfusion pressure, or arterial and mixed venous blood gases. However, after 9 minutes of chest compression, significant differences were noted between the ventilated and nonventilated groups. The nonventilated group had significantly (P< .05) lower mean arterial PO2(38 ± 17 mm Hg compared with 216 ± 104 mm Hg) and higher PCO2(62 ± 16 mm Hg compared with 35 ± 8 mm Hg), lower mixed venous PO2(15 ± 7 mm Hg compared with 60 ± 7 mm Hg). Nine of 12 (75%) of the ventilated animals, and only 1 of 12 (8%) of the nonventilated animals had return of spontaneous circulation after cardiac arrest (P< .002).ConclusionsIn this animal model of cardiac arrest, ventilation was important for resuscitation. The importance of ventilation could be related to the prolonged duration of untreated ventricular fibrillation and the significantly greater hypoxia and hypercarbic acidosis found in the nonventilated animals.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundFear of infection limits the willingness of laymen to do cardiopulmonary resuscitation (CPR). This study assessed the time course of change in arterial blood gases during resuscitation with only chest compression (no ventilation) in an effort to identify the time for which ventilation could be deferred.Methods and ResultsAortic pressures and arterial blood gases were monitored in seven 20- to 30-kg dogs in ventricular fibrillation (VF) at 2-minute intervals during chest compression alone (no ventilation) at 80 to 100 compressions per minute. Before the induction of ventricular fibrillation, all animals were intubated and ventilated with room air, 10 mL/kg. The endotracheal tube was removed when VF was induced. Pre-VF arterial pH, PCO2, and O2saturation were (mean ± SEM) 7.39 ± 0.02, 27.0 ± 1.5 mm Hg, and 97.5 ± 0.5%, respectively, with aortic pressures being 143.2 ± 5.7/116.2 ± 4.6 mm Hg. At 4 minutes of chest compression alone, the corresponding values were 7.39 ± 0.03, 24.3 ± 3.1 mm Hg, and 93.9 ± 3.0%, with an arterial pressure of 48.1 ± 7.7/22.6 ± 3.9 mm Hg. Mean minute ventilation during the fourth minute of CPR, measured with a face mask-pneumotachometer, was 5.2 ± 1.1 L/min.ConclusionsThese data suggest that in the dog model of witnessed arrest, chest compression alone during CPR can maintain adequate gas exchange to sustain O2saturation > 90% for > 4 minutes. The need for immediate ventilation during witnessed arrest should be reexamined.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID