Hours Of Coronary Artery Occlusion Research Articles

Therapeutic Hypothermia Reduces the Inflammatory Response Following Ischemia/Reperfusion Injury in Rat Hearts.

Therapeutic hypothermia (TH) is known to protect against ischemia/reperfusion (I/R) injury. One mechanism of I/R injury includes secondary injury due to the inflammatory cascade. We hypothesized that TH reduces the inflammatory response following I/R injury. Rats were randomized to sham, normothermic, or hypothermic groups and subjected to 1 hour of coronary artery occlusion and 48 hours of reperfusion. Hypothermia was initiated, using the ThermoSuit® device, 2 minutes after the onset of coronary artery occlusion to a core temperature of 32°C, and then the rats were allowed to rewarm. After 48 hours, rats in the hypothermia group demonstrated a preserved left ventricular fractional shortening by echocardiography. TH decreased the inflammatory cytokines in the risk zone of the heart, which included monocyte chemoattractant protein-1, interleukin-6, tumor necrosis factor-α, and inducible nitric oxide synthase gene expression, and altered expression of the remodeling genes of matrix metalloproteinase and tissue inhibitor of metalloproteinase. Furthermore, rat inflammatory cytokines & receptors PCR array was performed and the data showed that 71 out of 84 genes were upregulated in the risk zone of normothermia hearts versus shams. The upregulation was largely reversed in the risk zone of hypothermia hearts compared to normothermia. TH preserves cardiac function, decreases excessive inflammatory gene expression, and regulates myocardial matrix remodeling related genes.

Mechanisms underlying Endothelin‐1 effects on ischemic ventricular tachycardia in canine myocardium

Background: Endothelin‐1(ET‐1) induces ventricular tachycardia (VT), possibly by promoting triggered activity (TA). We studied ET‐1 and the ET‐A receptor blocker, BQ123, in a model of focal or reentrant VT, to test the hypothesis that focal VT and TA were selectively affected. Methods: Anesthetized dogs (n=38) with 1‐3 hours of coronary artery occlusion underwent 3‐D activation mapping to identify mechanisms of VT. If VT was not inducible, ET‐1 (0.15–0.45 mcg/kg IV) was infused. If VT was reproducibly induced at baseline, BQ123 (2.5 mcg/kg IV) was given. Effects on action potential (AP), delayed and early afterdepolarizations (DADs and EADs), and TA of ischemic endocardium were studied in vitro with microelectrodes. Results: Of 15 dogs without VT, ET‐1 promoted induction of VT of mixed reentrant and focal origin in 5 (p<0.05 (*) vs. saline alone). In 11 dogs, BQ123 prevented reentrant VT in 4 of 6* vs. 0/5 with focal VT. ET‐1 and BQ123 infusion did not change effective refractory period, pacing threshold, mean arterial pressure, or infarct size. In vitro, ET‐1 infusion did not induce and BQ123 did not prevent EADs, DADs, or TA but ET‐1 superfusion with rapid pacing produced AP alternans in 8 of 15 tissues. Conclusions: ET‐1 promotes focal and reentrant VT but ischemic sites in vitro did not show TA. BQ123 preferentially blocked reentrant VT. The effect of ET‐1 on ischemic reentrant VT may be mediated by triggering AP alternans.

Uncertainty on the Use of Aldosterone Antagonists for Primary Therapy for Sudden Cardiac Death in the Setting of Implanted Devices

In the early development of therapy for acute myocardial infarction, it was thought that once the necrotic process had been completed (usually within 24 hours of coronary artery occlusion), additional therapies could not affect outcome. However, after completion of the necrotic process, the myocardial infarction may thin and stretch (involving lengthwise slippage of myocytes), a phenomenon referred to as myocardial infarct expansion. This process causes local left ventricular cavity dilatation followed by gradual global left ventricular dilatation and lengthwise (eccentric) hypertrophy of the noninfarcted tissue. Apoptosis (programmed cell death) and some attempt of the myocardium to regenerate, especially at the infarct border zone, may also contribute to this remodeling process of the ventricle. If the left ventricle remodels in such a way that it becomes very dilated, then the prognosis is poor, and heart failure is more likely to occur.1 These later processes of myocardial infarct expansion and left ventricular remodeling became the target of therapies such as angiotensin-converting enzyme (ACE) inhibition that could be initiated after 24 hours of coronary occlusion. ACE inhibition, angiotensin receptor blockade, and long-term β-blockade have become standard pharmacological approaches for postinfarction left ventricular dysfunction and heart failure. Response by Pitt and Pitt p 2989 Ventricular arrhythmias can occur in both the acute and chronic phases of acute myocardial infarction and can lead to sudden cardiac death (SCD). Reentrant arrhythmias may arise at the border zone of infarcts, causing monomorphic ventricular tachycardia that may occur years after the index infarction. Recurrent myocardial ischemia resulting in an unstable substrate may contribute to polymorphic ventricular tachycardia or ventricular fibrillation. Agents such as β-blockers that are anti-ischemic may reduce sudden death by quieting this unstable substrate. In the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II, implantable defibrillators were shown to reduce mortality in post–myocardial infarction patients with …

Adrenoceptor Blockers and Focal Ventricular Tachycardia during Coronary Artery Occlusion

Background Ventricular tachycardia (VT) of focal endocardial and Purkinje origin occurs in humans. Pharmacological blockade of adrenoceptors on endocardial tissues may selectively prevent the induction of focal VT. We tested the hypothesis that alpha adrenoceptor blocker WB4101(WB), beta-1 receptor blocker Metoprolol (Met) and beta-2 receptor blocker ICI 118,511(ICI) prevent the induction of focal ischemic VT and evaluated possible mechanisms. Methods 50 alpha chloralose anesthetized dogs with 1-4 hours of coronary artery occlusion were involved. 23 multipolar plunge electrodes were placed in and surrounding the risk zone of anterior descending coronary artery. 3-D activation mapping off line helped to identify the origin of VT. If VT was reproducibly induced, WB (0.3ug/kg), Met (1mg/kg) or ICI (0.2mg/kg) were given. The effects of blockers on delayed afterdepolarizations (DADs) and triggered activity (TA) recorded from endocardium and Purkinje tissue excised from the focal origin of VT were studied in vitro by standard microelectrode techniques. Results Eleven dogs were given WB, 2 had VTs blocked with the same or more extrastimuli. Twelve dogs were received ICI, only 3 had VT blocked, which were no different compared to focal endocardial or Purkinje VTin dogs with saline treatment of which 1 of 12 had apparent block (p=ns). However, seven of 15 dogs given Met had focal VT blocked, which was different from the saline treated (p< 0.05). Of tissues at the origin of VT, excised and studied in vitro, all foci showed DADs and TA with ISO which were were blocked by WB (10-7 M, in 2 of 6, p=ns), ICI (10-7 M, in 0 of 4, p=ns) and Met (10-7 M, in 6 of 8, p<0.05 vs control). Conclusions Pharmacological blockade of beta-1 adrenoceptor in acute ischemia selectively prevents induction of focal VT due to DADs and TA but alpha adrenoceptor and beta-2 receptor blockade does not.

Changes in Myocardial Electrical Impedance Induced by Coronary Artery Occlusion in Pigs With and Without Preconditioning

Myocardial ischemia increases tissue electrical resistivity leading to cell-to-cell uncoupling, and this effect is delayed by ischemic preconditioning in isolated myocardium. Alterations in myocardial resistivity elicited by ischemia in vivo may influence arrhythmogenesis and local ST-segment changes, but this is not well known. Myocardial impedance (resistivity [omega x cm] and phase angle [degrees]), epicardial ST segment, and ventricular arrhythmias were analyzed during 4 hours of coronary artery occlusion in 11 anesthetized open-chest pigs; these were compared with 13 other pigs submitted to a similar coronary occlusion preceded by ischemic preconditioning. Myocardial resistivity rose slowly during the first 34+/-7 minutes of occlusion (237+/-41 to 359+/-59 omega x cm), increased rapidly to 488+/-100 omega x cm at 60 minutes, and reached a plateau value (718+/-266 omega x cm, ANOVA; P<.01) at 150+/-69 minutes. By contrast, phase-angle changes began after 17 minutes of ischemia (-3.0+/-1.6 degrees to -4.2+/-1.2 degrees at 29+/-8 minutes) and evolved faster thereafter (-12.5+/-5.3 degrees at 144+/-56 minutes). Marked changes in myocardial impedance were observed during the reversion of ST-segment elevation that occurred 1 to 4 hours after occlusion, but impedance changes were less apparent during the early ST-segment recovery seen at 15 to 35 minutes of ischemia. The second arrhythmia peak (30+/-5 minutes) coincided with the fast change in tissue impedance, and both were delayed (P<.05) by ischemic preconditioning. A rapid impairment of myocardial impedance occurs after 30 minutes of coronary occlusion, and its onset is better defined by shift in phase angle than by rise in tissue resistivity. Phase 1b arrhythmias are associated with marked impedance changes, and both are delayed by preconditioning. Reversion of ST-segment elevation is partially associated with impairment of myocardial impedance, but other factors play a role as well.

Gender does not influence acute myocardial infarction in adult dogs

Mechanisms responsible for the well-documented “protection” against myocardial ischemia and infarction in young women and subsequent loss of protection after menopause remain speculative. One possibility is that gender-related variables (such as endogenous hormone levels or regular loss of stored iron) alter the susceptibility of the heart to ischemia: if so, then premenopausal women when compared with men may manifest endogenous protection against acute myocardial ischemic injury. Using the canine model we therefore sought to determine whether gender influences acute myocardial ischemia and infarction. Retrospective analysis was performed on data compiled from 60 mature adult dogs subjected to 1 hour of coronary artery occlusion and ≥4 hours of reperfusion. We first compared the incidence of lethal ventricular fibrillation in the male and female cohorts and then for survivors compared collateral blood flow during coronary occlusion (by injection of radioactive microspheres), infarct size (assessed by tetrazolium staining and expressed as a percentage of the myocardium at risk), and regional wall motion (by somomicrometry) in the infarct-related area. The incidence of lethal ventricular fibrillation was 23% in the male dogs and 19% in the female dogs ( p = 0.70, difference not significant). For survivors, the area at risk of infarction was comparable in males and females (23 ± 2% and 22% ± 1% of the total left ventricular weight), and the groups were equally ischemic during coronary occlusion, with collateral blood flow to the ischemic subendocardium averaging 0.05 ± 0.02 and 0.07 ± 0.01 ml/min/g tissue. There was no difference in infarct size between the two cohorts: area of necrosis was 17% ± 6% and 18% ± 3% of the myocardium at risk in the males and females, respectively. In addition, the groups were equally dyskinetic during occlusion and equally hypokinetic after reperfusion. We conclude that gender does not influence acute myocardial ischemia and infarction in the canine model.

1005-78 Myocardial Preconditioning by Laser Irradiation

We previously demonstrated that transmural laser channels made after coronary occlusion did not acutely enhance blood flow or reduce infarct size. In contrast, other studies (which did not measure blood flow) reported increased survival and/or reduction of necrosis when laser channels were made prior to coronary occlusion. To reconcile this apparent paradox, we speculated that laser channels made prior to occlusion might protect the heart via a mechanism independent of blood flow. To test this hypothesis, we randomized 12 rats to either; (1) control: 1 hour of coronary artery occlusion followed by 5 hours of reperiusion. or (2) laser: 6 non-transmural channels were made in the anterior wall of the left ventricle using a holmium:YAG laser coupled to a 400 micron diameter optic fiber. Two minutes after the last channel was made, the left coronary artery was occluded for 1 hour and then reperiused for 5 hours. We monitored lead I of the ECG and noted the incidence of ventricular tachycardia (VT) and fibrillation (VF). At the end of the protocol. the artery was briefly reoccluded and we determined the area at risk (AR) by injection of pigment into the circulation. Heart slices were incubated in triphenyltetrazolium chloride solution to delineate the area of necrosis (AN), which was expressed as a percent of area at risk (AN/AR). [data given as mean ± SEM]Empty CellARAN/ARVT/vFControl49 ± 361 ± 95Laser45 ± 535 ± 4*0**p &lt; 0.03 versus control p &lt; 0.03 versus control Although laser channels were associated with thermally-induced necrosis, total infarct size was smaller in laser-treated hearts. Protection of muscle was most prominent in heart slices containing laser channels. but also occurred in slices without channels. Laser treatment also significantly reduced the incidence of VT and VF. In conclusion, non-transmural laser channels “preconditioned” the heart against subsequent ischemia. Although the mechanism of protection is unknown, it cannot be attributed to increased blood flow to the tissue because the channels did not connect to the ventricular cavity.

Dobutamine echocardiography for determining the extent of myocardial salvage after reperfusion. An experimental evaluation.

Although dobutamine echocardiography is being increasingly used to determine the presence of viable myocardium in patients who have undergone successful reperfusion therapy, the physiological basis for such a use has not been clearly defined. Because postischemic myocardium has contractile reserve, we hypothesized that the absolute degree of wall thickening induced by dobutamine during reflow would be directly related to the amount of myocardium that has escaped necrosis. Three groups of 12 dogs each were studied at baseline and during 2 to 6 hours of coronary artery occlusion and 15 minutes of reperfusion. In group 1 dogs, which did not receive dobutamine during any of these stages, percent wall thickening at these stages was 32 +/- 6%, -2 +/- 6%, and 5 +/- 6%, respectively, and there was no relation between infarct size and percent wall thickening during reflow (r = .20, P = .51). In group 2 dogs, which received 15 micrograms/kg per minute of dobutamine at all stages, wall thickening at these stages was 40 +/- 8%, 0 +/- 8%, and 19 +/- 10%, respectively, and a good inverse correlation was noted between infarct size and percent wall thickening during reflow (r = -.81, P = .001). In group 3 dogs, in which wall thickening during reflow was measured both before and during infusion of 15 micrograms/kg per minute of dobutamine, it was 5 +/- 8% and 18 +/- 14%, respectively, at these stages. Although the correlation between infarct size and percent wall thickening was poor in the absence of dobutamine (r = .36, P = .26), an excellent inverse correlation was noted between the two in the presence of dobutamine (r = -.93, P < .001). A fair inverse correlation was also noted between infarct size and the absolute change in wall thickening induced by dobutamine (r = -.72, P < .01). Maximal wall thickening was noted at a dobutamine dose of 15 micrograms/kg per minute, and lower doses did not elicit thickening in the presence of larger infarcts despite the presence of viable myocardium. When myocardial necrosis coexists with post-ischemic myocardial dysfunction and no residual coronary stenosis, the absolute degree of wall thickening during dobutamine can be used to determine the extent of myocardium that has escaped necrosis. The dose of dobutamine needed to elicit maximal thickening of the postischemic myocardium is related to the amount of myocardial necrosis.

Ischemie preconditioning and long-chain acyl carnitine in the canine heart

This study investigated the effects of ischemic preconditioning on myocardial carnitine-linked metabolism and high-energy phosphates in the canine model of ischemia and reperfusion. Anesthetized dogs underwent 1 hour of coronary artery occlusion and 4.5 hours of reperfusion. The dogs were randomly assigned to a control group (no intervention for 30 minutes), a preconditioned group (four repeated episodes of 3 minutes of mechanical coronary occlusion, each followed by 5 minutes of reperfusion), and a coronary cyclic flow variation (CFV) group (coronary artery stenosis and endothelial injury, resulting in an average of four episodes of platelet thrombosis and dislodgment). After completion of the protocol, ATP, creatine phosphate, and long-chain acyl carnitine concentrations were studied in both nonischemic and previously ischemic myocardium. In Part I of this study (Ovize et al., Circulation 1992, 85:779-789), it was reported that both mechanical occlusion and CFV before sustained occlusion resulted in a decrease in infarct size. In the present paper, we report changes in high-energy phosphates and long-chain acyl carnitine in these groups. Control, preconditioned, and CFV groups showed similar depletion in ATP content and "overshoot" in creatine phosphate stores. Control dogs exhibited a significant accumulation of long-chain acyl carnitine in the previously ischemic tissue (219 +/- 61 vs 131 +/- 38 nmoles/g wet weight in the nonischemic tissue; P < 0.05). No significant increase in long-chain acyl carnitine occurred in the mechanically preconditioned and CFV groups. These results indicate that brief episodes of transient ischemia before sustained coronary occlusion prevent long-chain acyl carnitine accumulation in the ischemic and reperfused canine myocardium.

Functional recovery after reperfusion is predicated on recovery of myocardial oxidative metabolism

To test the hypothesis that recovery of myocardial oxidative metabolism (MVO 2) is a necessary prerequisite for recovery of contractile function following reperfusion and to evaluate its dependency on the interval of antecedent ischemia before reflow, we evaluated 11 dogs serially for 4 weeks. Six dogs were subjected to prompt reperfusion (after 1 hour of coronary artery occlusion) and five were subjected to delayed reperfusion (after 4 hours of ischemia). Despite equivalent levels of myocardial blood flow with reperfusion, hearts subjected to prompt reperfusion had faster and more complete recovery of MVO 2 (assessed by sequential positron emission tomography with [ 11C]acetate) and function (assessed by echocardiography) compared with dogs subjected to delayed reperfusion. Infarct size was diminished in dogs with prompt reperfusion. In all dogs, recovery of function with reperfusion was predicted and correlated with early recovery of MVO 2 ( r = 0.61, p < 0.04). The results demonstrate that prompt reperfusion is associated with more rapid and complete recovery of oxidative metabolism and function and support the hypothesis that the ability to metabolize substrate oxidatively is a necessary prerequisite for recovery of function.

Salvage of ischemic myocardium by nonsynchronized retroperfusion in the pig

Salvage of ischemic myocardium, with the aid of a nonsynchronized coronary sinus retroperfusion system, was studied in a pig infarct model. In anesthetized open chested animals, the left anterior descending coronary artery was occluded for 4 hours and then reperfused for 1 hour before the animals were killed. In the control group (n = 12) no therapy was used. In the experimental group (n = 13), nonsynchronized retrovenous coronary sinus perfusion was applied during the 4 hours of coronary artery occlusion. Therapy consisted of intermittent balloon occlusion of the coronary sinus (5-second inflation, 5-second deflation) with retroperfusion of arterial blood at 60 ml/min during the inflation part of the cycle. Infarct size, expressed as a percentage of the area at risk (+/- standard deviation), was significantly smaller in the experimental group (41.5% +/- 15.0%) than in the control group (80.5% +/- 6.1%) (p less than 0.001). Mean coronary sinus pressure (+/- standard deviation) was 51 +/- 12 mm Hg in the experimental group but was not elevated in the control animals. We conclude that nonsynchronized retrovenous coronary sinus perfusion was able to significantly salvage ischemic myocardium in a model of minimal intercoronary collateral circulation.

One hour of myocardial ischemia decreases the activity of the stimulatory guanine-nucleotide regulatory protein Gs.

The effect of 1 hour of myocardial ischemia on the function of the stimulatory guanine-nucleotide-binding protein Gs was examined. This study follows our recent finding that myocardial ischemia increases the density of beta-adrenoreceptors in a conscious canine model while having the opposite effect on the activity of adenylate cyclase. Coronary artery occlusion was induced in five conscious dogs and verified by measurement of blood flow using the Doppler and microsphere techniques. Alterations in the level and function of Gs were examined in sarcolemmal membranes prepared from ischemic and nonischemic regions of the left ventricle. After 1 hour of coronary artery occlusion, the functional activity of sarcolemmal Gs, as determined by reconstitution with cyc- membranes, decreased by 27 +/- 7% in the ischemic zone. Cholera toxin labeling performed in parallel with the reconstitution studies demonstrated a similar decrease of 28 +/- 7%. This was associated with decreases in basal activity and decreases in adenylate cyclase activity stimulated by GTP, GTP plus isoproterenol, sodium fluoride, and forskolin. Thus, a defect distal to the beta-adrenoreceptor occurs in the transduction of adrenergic signals to the heart as a consequence of 1 hour of ischemia.

A physiologically based model of creatine kinase-MB release in reperfusion of acute myocardial infarction

To gain insight into the altered kinetics of creatine kinase-MB (CK-MB) release after reperfusion, a physiologically based model with first-order CK-MB appearance and disappearance functions was postulated. This biexponential model is based on the assumption that reperfusion reestablishes nutritive blood flow, providing direct access of interstitial CK-MB to the bloodstream. This is in contrast to persistent coronary artery occlusion, in which no direct access to nutritive flow is present. The accuracy of this model was examined in 8 dogs reperfused after 2 hours of coronary artery occlusion. The fit to observed values was excellent, with a mean r 2 of 0.97 ± 0.05. In agreement with the biexponential model, the initial increase in CK-MB activity was abrupt and rapid. The same degree of accuracy was found in 21 patients with angiographic evidence of reperfusion after thrombolytic therapy (mean r 2 0.97 ± 0.02). The appearance characteristics were similar to the animal model, with an abrupt and rapid increase in CK-MB activity. When compared with 5 patients with persistent occlusion, k a, the rate constant of the appearance function, clearly distinguished patients with reperfusion (chi-square = 20.6, p < 0.0001), whereas considerable overlap was present in the time to peak CK-MB (time to peak <12 hours, chi-square = 3.6, difference not significant). Alterations of CK-MB release in reperfusion can be accurately modeled with the biexponential model. The characteristics of this model suggest that early identification of reperfusion by serial CK-MB assay is possible.

Reduction in infarct size by the prostacyclin analogue iloprost (ZK 36374) after experimental coronary artery occlusion-reperfusion

In this study we attempted to determine whether administration of iloprost (ZK 36374), a chemically stable prostacyclin analogue, would reduce infarct size after experimental coronary artery occlusion and reperfusion. One hour of coronary artery occlusion was performed in 28 open-chest, anesthetized rabbits, followed by 5 hours of reperfusion. Two minutes after occlusion, 99mTc-labeled albumin microspheres were injected into the left atrium for later assessment of the area at risk of infarction. Fifteen minutes after occlusion animals were randomly assigned to either the treatment group (iloprost, 1.2 μg/kg/min intravenously for 6 hours; n = 14) or the control group (n = 14). In vitro platelet aggregation was inhibited in rabbits receiving iloprost. In 10 rabbits (five treated and five control) regional myocardial blood flow was also measured by means of differentially labeled radioactive microspheres. Infarct size was significantly smaller in treated rabbits (53.6 ± 4.1% of the risk zone vs 89.4 ± 3.8% in control rabbits; p < 0.001). Flow to the nonischemic myocardium was higher in treated animals, that is, 1.87 ± 0.20 ml/min/gm of tissue 50 minutes after occlusion and 1.90 ± 0.20 ml/min/gm of tissue 4 hours after reperfusion, compared with 1.54 ± 0.20 and 1.64 ± 0.30 ml/min/gm of tissue, respectively, in control rabbits ( p < 0.01). Collateral flow to the ischemic region was not affected by the drug. Mean arterial blood pressure, heart rate, and pressure-rate product in treated rabbits were not significantly different from values in control rabbits. In conclusion, administration of iloprost reduced myocardial infarct size in this model of myocardial ischemia and reperfusion in absence of major hemodynamic effects.

Effects of calcium antagonists on infarcting myocardium

Numerous studies have been conducted over the past 10 years on the effects of calcium antagonists on regional myocardial ischemia and infarct size. Verapamil, for example, reduced the degree of adenosine triphosphate degradation during 15 minutes of coronary occlusion followed by reperfusion in an anesthetized canine preparation. It also preserved the ultrastructural appearance of mitochondria in myocardium subjected to 1 hour of ischemia. Using an 8-hour permanent coronary artery occlusion model in which risk zone was assessed with radioactive microspheres and infarct size determined by tetrazolium staining, verapamil, administered 1 hour after occlusion, resulted in a modest decrease in infarct size. In a reperfusion model in which anesthetized dogs were subjected to 3 hours of coronary artery occlusion followed by 3 hours of reperfusion, verapamil decreased infarct size when it was administered during the period of ischemia, but failed to decrease infarct size when administered only during the reperfusion phase, i.e., after 3 hours of ischemia. Although verapamil is known to have negative inotropic effects, the newer calcium antagonist agent nisoldipine is less negatively inotropic, and might therefore be preferable in the situation of compromised hemodynamics. In a 6-hour permanent coronary artery occlusion model, nisoldipine decreased infarct size without decreasing left ventricular contractility. Most published reports support the concept that calcium antagonists decrease infarct size in models of experimental infarction. Of 4 major clinical studies, only 1 has shown that calcium antagonists are capable of reducing infarct size in man. However, in most of these studies, drug therapy commenced relatively late—4 or more hours after symptoms. In order for these drugs to demonstrate beneficial effects, the risk zone may have to be small and the degree of collateral flow adequate, the drug may have to be given very early or even before coronary occlusion (in a prophylactic fashion) and administration of the drug may have to be coupled to early coronary reperfusion.

Effect of verapamil on infarct size in dogs subjected to coronary artery occlusion with transient reperfusion

Reocclusion after successful coronary reperfusion occurs in 15 to 35% of patients receiving thrombolytic therapy for acute myocardial infarction. The present study was designed to simulate the clinical situation of reocclusion and determine whether verapamil might be effective in reducing myocardial necrosis and preserving high energy phosphates in this setting. Pentobarbital-anesthetized, open chest dogs underwent occlusion of the left anterior descending coronary artery for 2 hours followed by 1 hour of reperfusion and a further 4 hours of coronary artery occlusion. Treatment with verapamil (intravenous bolus dose of 0.2 mg/kg body weight followed by infusion of 0.56 +/- 0.14 mg/kg per h) was begun 1 hour after occlusion and infusion was continued for the remainder of the experiment. The dose of verapamil was adjusted to lower mean arterial pressure to approximately 90 mm Hg. The area at risk was determined by intraatrial injection of monastral blue dye and the area of necrosis was assessed by triphenyltetrazolium chloride staining. In vivo myocardial needle biopsy for determination of adenosine triphosphate and creatine phosphate was performed at the end of the experiment. The area of the left ventricle at risk was similar in both groups (control [n = 8], 20.2 +/- 1.6% versus verapamil-treated [n = 9], 23.1 +/- 2.9%; p = NS). The area of necrosis expressed as a percent of the area at risk was reduced in the verapamil-treated group compared with the control group (43.3 +/- 5.0% versus 63.1 +/- 6.8%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical Revascularization of Acute (1 Hour) Coronary Occlusion: Blood versus Crystalloid Cardioplegia

This study compares blood versus crystalloid cardioplegia in restoring contractile function, and high-energy phosphate and tissue water content in a myocardial segment after 1 hour of coronary artery occlusion. Anesthetized dogs underwent instrumentation with the chest open to measure left ventricular and aortic pressures, and systolic shortening in the myocardium perfused by the left anterior descending coronary artery (LAD) was measured with ultrasonic crystals. In 21 dogs, the LAD was occluded for an hour, thereby replacing systolic shortening with passive lengthening averaging −28.7 ± 6.2% of control shortening in both groups. The dogs were then placed on total bypass, and arrest was achieved with multidose crystalloid (N = 10) or blood cardioplegia (N = 11). The ligatures were released just prior to the second infusion of cardioplegic solution. Postischemic subendocardial levels of adenosine triphosphate were comparably depleted with crystalloid and blood cardioplegia (55.2% and 44.0%, respectively, of control). Subendocardial increases in water content were similar for crystalloid (3.62%) and blood (3.16%) cardioplegia. Recovery of segmental shortening was significantly greater with blood than crystalloid cardioplegia (31.5 ± 8.2% versus 4.9 ± 6.6% of control, respectively). We conclude that the composition and the delivery of blood cardioplegia used in this study restore greater postischemic function than crystalloid cardioplegia in acute evolving myocardial infarction.

Occlusive and reperfused myocardial infarcts: effect of Gd-DTPA on ECG-gated MR imaging.

In vivo magnetic resonance (MR) imaging was performed to determine the effect of gadolinium-DTPA on MR intensity and relaxation times of occlusive and reperfused acute myocardial infarcts. In 18 dogs the left anterior descending (LAD) coronary artery was ligated. Five hours after LAD artery occlusion, six dogs in group 1 received intravenous Gd-DTPA, 0.5 mmol/kg, and 6 dogs in group 2 received 0.1 mmol/kg. The myocardia of the remaining six dogs (group 3) were reperfused after 1 hour of coronary artery occlusion; these dogs received 0.1 mmol/kg Gd-DTPA intravenously 5 hours later. MR imaging was performed before (control) and 5 minutes after Gd-DTPA administration. Intravenous administration of 0.1 mmol/kg Gd-DTPA significantly improved contrast between infarcted and normal myocardium on T1-weighted spin echo images in group 3. In all groups, T2-weighted precontrast images provided contrast between infarcted and normal myocardium equivalent or better than that provided by T1-weighted postcontrast images. Thus, Gd-DTPA did not improve contrast between ischemically injured and normal myocardium in the early hours after coronary artery occlusion.

Lack of spontaneous or verapamil-induced salvage of potentially necrotic myocardium following 24 hours of coronary artery occlusion in the rabbit

Lack of spontaneous or verapamil-induced salvage of potentially necrotic myocardium following 24 hours of coronary artery occlusion in the rabbit

Anipamil limits myocardial necrosis in the closed chest dog doring 24 hours of coronary artery occlusion

Anipamil limits myocardial necrosis in the closed chest dog doring 24 hours of coronary artery occlusion