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Biomedical subjects

M V Cohen

Publications and source records attributed to M V Cohen.

At least 91 records · Page 5Linked to original sources
PubMed1994

Dobutamine echocardiography and resting-redistribution thallium-201 scintigraphy predicts recovery of hibernating myocardium after coronary revascularization.

The value of dobutamine echocardiography and resting thallium-201 scintigraphy to predict reversal of regional left ventricular wall motion dysfunction after revascularization in patients with chronic coronary artery disease was assessed. Improvement in wall motion during dobutamine echocardiography and normal or mildly decreased uptake on thallium-201 scanning are strong predictors of reversible left ventricular dysfunction. Dobutamine echocardiography and resting thallium-201 scanning are simple and safe methods of assessing hibernating myocardium.

Angioplasty, Balloon, Coronary↗
PubMed1994

A new animal model of controlled coronary artery occlusion in conscious rabbits.

OBJECTIVE: The aim was to develop a method for installing a pneumatic occluder on the coronary artery of a rabbit, and to see whether repetitive coronary occlusions could induce collateral development as in dogs. METHODS: A superficial branch of the left coronary artery was encircled with a balloon occluder, and a catheter was inserted into the left atrial appendage of New Zealand White rabbits, with a survival rate of 89.5%. Baseline collateral flow was measured 5-7 d after surgery with radioactive microspheres while the artery was occluded. According to a predetermined schedule animals were assigned to control and experimental groups. In the latter the balloon was inflated for 2 min once every 15 min for 8 h per d, 5 d per week. Collateral flow measurements were repeated after 100 and 300 occlusions. In control animals repeat flow measurements were made approximately 4 and 14 d after the first determination. RESULTS: Inflation of the balloon occluder reliably resulted in marked S-T segment elevation which quickly resolved after balloon deflation. These changes were nearly identical after two weeks of observation. Average baseline collateral flows in both groups were less than 5% of normal myocardial flow. There was no appreciable change during the two week period of observation in either control rabbits or those receiving at least 300 2 min coronary occlusions. CONCLUSIONS: The rabbit tolerates implantation of a pneumatic coronary occluder without noticeable problem and can successfully serve as a small animal model of repetitive or chronic myocardial ischaemia. The surgical preparation is not difficult, and ischaemia can be reproducibly created and relieved for at least three weeks following surgery. Coronary collaterals are sparse in the rabbit, and repetitive occlusions can be instituted without the complication of collateral development.

Animals↗
PubMed1994

Acadesine extends the window of protection afforded by ischaemic preconditioning.

OBJECTIVE: The aim was to test whether acadesine (5-amino-4-imidazolecarboxamide riboside, AICAR), an adenosine regulating agent which increases tissue adenosine during ischaemia, could prolong the window of protection from ischaemic preconditioning. METHODS: A branch of the left coronary artery of a rabbit heart was occluded for 30 min and reperfused for 180 min to induce infarction. Infarct size was determined with triphenyl tetrazolium staining. Prior to the 30 min ischaemia, rabbits were subjected to one of the following seven protocols: (1) No treatment (controls). (2) Preconditioning with 5 min of regional ischaemia followed by 2 h of reperfusion. (3) Treatment with acadesine (2.5 mg.kg-1.min-1 intravenously for 5 min starting 155 min prior to 30 min ischaemia followed by 210 min infusion of 0.5 mg.kg-1.min-1. (4) Treatment with acadesine (same schedule as in group 3) plus preconditioning as in group 2. (5) Treatment with acadesine for a shorter period (acadesine 2.5 mg.kg-1.min-1 for 5 min starting 30 min prior to preconditioning followed by 0.5 mg.kg-1.min-1 for only 60 min) plus preconditioning as in group 2. (6) Treatment with preconditioning followed by adenosine receptor blockade with 8-(p-sulphophenyl)theophylline (SPT) 10 mg.kg-1 intravenously immediately after and again 15 min after preconditioning. (7) Treatment with short infusion of acadesine plus preconditioning plus SPT. RESULTS: Preconditioning followed by 2 h of reperfusion offered little protection against infarction [28.6(SEM 2.7)% of the ischaemic zone infarcted] as compared to control [38.7(3.1)% infarction]. Treatment with acadesine alone did not modify the infarct size [37.8(3.5)%], but both of the acadesine plus preconditioning groups showed a significant limitation of infarct size with 13.9(3.1)% infarction in group 4 and 12.7(2.2)% infarction in group 5 (both p < 0.01 v control). Although SPT alone did not modify the infarct size [26.8(3.3)%], SPT blocked the protective effect of acadesine [25.3(2.9)%, p < 0.05 v group 5]. CONCLUSION: Acadesine can delay the natural decay of preconditioning. This delay appeared to be mediated by adenosine and may have therapeutic potential.

Adenosine↗
PubMed1994

Ketamine-xylazine anaesthesia permits a KATP channel antagonist to attenuate preconditioning in rabbit myocardium.

OBJECTIVE: ATP sensitive potassium (KATP) channels have been implicated in the mechanism of ischaemic preconditioning, though apparently not in the pentobarbitone anaesthetised rabbit model. The aim of this study was to test whether potassium channel activation and blockade would alter protection in ketamine-xylazine anaesthetised rabbits. METHODS: In situ rabbit hearts (n = 50) received 30 min regional ischaemia and 3 h reperfusion. Some hearts were preconditioned by 5 min regional ischaemia and 10 min reperfusion prior to the long ischaemia. Infarct size was determined by tetrazolium staining. RESULTS: In rabbits anaesthetised with ketamine-xylazine, brief preconditioning ischaemia continued to produce much smaller infarcts than in non-preconditioned animals [19(SEM 2)% v 47(3)%, p < or = 0.05]. blocking KATP channels by pretreating with glibenclamide resulted in 35(3)% infarction in non-preconditioned hearts and aborted protection in preconditioned hearts [35(4)% infarction]. Substituting the potassium channel activator pinacidil for the short ischaemia caused comparable reductions in infarct size [28(4)%, p < or = 0.05 v non-preconditioned hearts]. This protection, however, could be blocked by concomitant administration of the adenosine receptor blocker 8-(p-sulphophenyl)theophylline (SPT) [44(3)% infarction]. CONCLUSIONS: When ketamine-xylazine anaesthesia was employed, the protective effects of ischaemic preconditioning in the rabbit heart could be blocked by glibenclamide, and pinacidil could mimic the protection of ischaemic preconditioning. Because the protection afforded by pinacidil could be blocked by SPT, however, there is still some question whether the KATP channel is the end effector of preconditioning.

Animals↗
PubMed1994

Rat and rabbit heart infarction: effects of anesthesia, perfusate, risk zone, and method of infarct sizing.

Rabbits and rats are becoming popular models for in vitro as well as in situ studies of myocardial infarction. In the present analysis we evaluated the results of several of our completed investigations and tested whether blood-free perfusate, anesthesia, or risk zone size affects infarction in these species. In addition, the influence of the method used for determining infarct size (histology or histochemistry) was examined in rabbits. All hearts experienced 30 min of regional ischemia followed by either 2-3 h of reperfusion in animals in which infarct size was assessed by staining with triphenyltetrazolium chloride or 72 h in those in which histological methods were used to measure infarct size. Eighteen rabbit and seven rat hearts perfused with Krebs buffer, seventeen open-chest rabbits, eight rats anesthetized with pentobarbital, and ten conscious rabbits were studied. Risk zone size measured with fluorescent particles was plotted against infarct size. Infarct size was linearly correlated with risk zone size and did not differ among models for each species. In rat hearts the regression line passed through the origin so that zero infarction occurred with zero risk zone size. However, in the rabbit heart there was no apparent infarction for risk zone sizes < 0.3 cm3. Although the relationship between risk zone and infarction was found to be remarkably independent of the model chosen, the nonzero intercept for the rabbit heart can be an important, previously unrecognized source of experimental variability when infarct size is expressed as a percentage of the risk zone.

Anesthesia↗
PubMed1994

Conscious rabbits become tolerant to multiple episodes of ischemic preconditioning.

Although ischemic preconditioning protects myocardium from infarction in isolated hearts and in anesthetized open-chest animals, its effects have not been examined in unanesthetized animals. Furthermore, it is unknown whether animals become tolerant to multiple episodes of ischemic preconditioning. Rabbits were chronically instrumented with a balloon occluder around a major branch of the left coronary artery for reversible coronary occlusion, a left atrial catheter for radioactive microsphere injections, ECG electrodes for monitoring of myocardial ischemia, and, in some cases, a carotid artery catheter for pressure measurements and timed withdrawal of reference arterial blood samples. Eight control rabbits underwent a 30-minute coronary occlusion and then 180 minutes of reperfusion. Five of the eight rabbits developed ventricular tachycardia or fibrillation during ischemia, and infarct size averaged 37.7 +/- 2.6% of the risk area. Eight rabbits experienced a 5-minute coronary occlusion and 10 minutes of reperfusion before the 30-minute occlusion. In these preconditioned animals, potentially fatal arrhythmias during ischemia were significantly reduced (one of eight, P < .05), and infarct size was much smaller (5.6 +/- 1.1%, P < .0001). The difference could not be explained by hemodynamics or collateral blood flow, which were nearly identical in the two groups. But when the 30-minute coronary occlusion was preceded by 40 to 65 five-minute occlusions during a 3- to 4-day period in seven animals, protection was markedly attenuated. Potentially lethal arrhythmias were very common, and infarct size averaged 26.5 +/- 2.9%, substantially larger than in rabbits with only one preconditioning occlusion (P < .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

alpha 1-adrenergic agonists precondition rabbit ischemic myocardium independent of adenosine by direct activation of protein kinase C.

Ischemic preconditioning in the rabbit is initiated by adenosine A1-receptor stimulation, which activates protein kinase C (PKC). Additionally, alpha 1-adrenergic agonists can similarly protect ischemic myocardium, but there has been confusion about the role adenosine receptors play in this protection. To characterize the interaction between adrenergic and adenosine receptors and to study the possible role of PKC in this protection, we used isolated rabbit hearts perfused with oxygenated Krebs' buffer. All hearts were subjected to 30 minutes of regional myocardial ischemia and 2 hours of reperfusion. Infarct size was determined by triphenyltetrazolium staining. Pharmacologic preconditioning in hearts with a 5-minute phenylephrine (PE) infusion 10 minutes before the prolonged regional ischemia resulted in significantly smaller infarcts (9.7 +/- 1.3% of risk area) than in control hearts (31.0 +/- 2.6%, P < .05). This protection could be effectively blocked by administration of the alpha-adrenergic blocker phenoxybenzamine. Methoxamine, an alpha 1a-selective agonist, failed to protect, whereas the alpha 1b-selective antagonist chloroethylclonidine aborted the protective effect of PE. Polymyxin B, an inhibitor of PKC, also blocked the protective effect of PE, implying that PKC has an important role in preconditioning. The adenosine receptor blocker 8-(p-sulfophenyl)theophylline (SPT) given at the same time as the PE infusion did not affect the protection, implying that an alpha 1-agonist could initiate protection independent of adenosine, presumably by direct coupling to PKC. However, the protective effect of PE could be blocked if SPT were administered during the 30-minute regional ischemia. This observation suggested that adenosine receptor occupancy is necessary during long ischemia to reactivate PKC and mediate the protection. However, the addition of a second PE infusion beginning 5 minutes before and continuing throughout the long ischemic period restored the protective effect of PE despite the presence of SPT. Thus, as long as at least one of the receptors (alpha 1-adrenegic or adenosine A1) is activated during long ischemia, protection will be realized. These data indicate that alpha 1 receptors do not precondition through an adenosine intermediate but that alpha 1-adrenergic and adenosine receptors activate parallel pathways within the myocyte that can trigger and mediate protection.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Age-associated changes in diastolic filling: Doppler E/A ratio is not associated with congestive heart failure in the elderly.

Although left ventricular filling tends to occur in late diastole in the elderly, the clinical significance of this change is unclear. To determine the prevalence of diastolic filling delay and its relationship to congestive heart failure (CHF) in the elderly, we studied 114 community-living elderly volunteers (median age 75, 37% male). Clinical history, physical examination, chest x-ray film, and Doppler echocardiogram were obtained in blinded fashion. CHF was diagnosed by a previously validated clinico-radiographic scoring system. Diastolic filling was assessed by the Doppler ratio of early to late transmitral flow velocity (E/A). The standard clinical definition of diastolic filling delay (E/A < 1) was met by 94 subjects (82%), and median E/A was 0.72; for this study, diastolic filling delay was defined at the median, although both approaches yielded similar results. Systolic function was normal (ejection fraction > or = 0.5) in 97%. There were 22 subjects (19%) with definite or possible CHF. Older subjects were more likely to have CHF, but not more likely to have an E/A ratio below the median. Subjects with diastolic filling delay were no more likely to have CHF than those without. Mean E/A was not different between CHF groups, and there was no significant correlation between E/A and CHF score. There was still no association after controlling for age, history of hypertension, and other potential confounders by multiple logistic regression. Although diastolic filling delay is common in the elderly, it does not correlate with signs and symptoms of CHF. Determination of its prognostic significance requires a prospective follow-up study.

Age Factors↗
PubMed1993

Factors influencing left ventricular systolic function in nonhypertensive morbidly obese patients, and effect of weight loss induced by gastroplasty.

Heart rate and blood pressure were measured, and echocardiography was performed in 39 patients whose actual body weight was greater than twice their ideal body weight to identify factors influencing left ventricular (LV) systolic function in morbidly obese patients and assess the effect of weight loss on LV systolic function. Patients were studied before and after weight loss induced by gastroplasty. The study cohort was 133 +/- 8% overweight before weight loss and 39 +/- 7% overweight at the nadir of weight loss. Before weight loss, LV fractional shortening varied inversely with LV internal dimension in diastole (an indirect index of preload), LV end-systolic wall stress and systolic blood pressure (indexes of afterload). The weight loss-induced change in LV fractional shortening varied directly with the pre-weight loss LV internal dimension in diastole, LV end-systolic wall stress and systolic blood pressure, and inversely with the pre-weight loss LV fractional shortening. The weight loss-induced change in LV fractional shortening varied inversely with the weight loss-induced changes in LV end-systolic stress and systolic blood pressure. In patients with reduced LV fractional shortening (n = 14), weight loss produced a significant increase in LV fractional shortening that was accompanied by a significant decrease in LV internal dimension in diastole, LV end-systolic stress and systolic blood pressure. The results suggest that LV loading conditions have an important role in determining LV systolic function in morbidly obese patients. Improvement in LV systolic function in these patients is closely related to weight loss-induced alterations in LV loading conditions.

Adult↗
PubMed1993

Myocardial ischemia is not a prerequisite for the stimulation of coronary collateral development.

To understand better the temporal sequence of coronary collateral development and the factors that may govern that development, dogs were chronically instrumented with left circumflex (LCf) Doppler flow probe, ameroid constrictor, balloon occluder, and left atrial and aortic catheters. Collateral blood flow was measured at least weekly or when the coronary artery occluded. The reactive hyperemic response (RH) to a 15-second LCf occlusion was recorded three times per week. Most LCf arteries occluded during the 4th week after surgery. Two patterns of coronary collateral development were observed. In 11 animals collateral flow did not change for 2 or 3 weeks; peak RH and flow debt repayment, indexes of coronary vascular reserve, changed little. The next week there was an abrupt increase in collateral flow from approximately 15% of normal to 100%. This increase was coincident with a sudden loss of coronary vascular reserve and therefore suggests myocardial ischemia was the principal stimulus. However, in 11 dogs collateral flow increased gradually over 3 to 4 weeks as indexes of RH slowly decreased. The greatest increase in collateral flow occurred while peak RH was still approximately twice baseline flow, representing 80% of peak flow measured 1 week after surgery. Therefore in these animals ischemia is less likely to have been the major stimulus of coronary collateral development.

Analysis of Variance↗
PubMed1993

Lack of effect of propranolol on canine coronary collateral development during progressive coronary stenosis and occlusion.

OBJECTIVE: The aim was to test the effect of propranolol, a beta adrenergic receptor blocking drug which diminishes myocardial ischaemia, on coronary collateral development. METHODS: Dogs were chronically instrumented with a left circumflex coronary artery Doppler flow probe, ameroid constrictor, pneumatic occluder, and left atrial and aortic catheters. Haemodynamic studies and measurements of normal myocardial and collateral blood flows were performed at least weekly after surgery, or sooner if the left circumflex artery occluded spontaneously, in eight control dogs and seven animals treated with propranolol, 240 mg twice daily (a dose which successfully attenuated the chronotropic effect of a graded infusion of isoprenaline). In dogs in which the left circumflex artery occluded within the first four weeks after surgery, collateral blood flow was measured during exercise on a motorized treadmill. RESULTS: There was no difference between the groups in the rate or pattern of coronary collateral development, magnitude of collateral flow before or after spontaneous left circumflex occlusion, and collateral vascular reserve during exercise. At the time of coronary occlusion resting collateral flow was equivalent to normal perfusion levels in both groups and averaged 87-96% of normal flows during exercise. CONCLUSIONS: Propranolol has no observable effect on coronary collateral development despite its acknowledged ability to prevent or attenuate myocardial ischaemia.

Animals↗
PubMed1993

The protection of ischaemic preconditioning can be reinstated in the rabbit heart after the initial protection has waned.

OBJECTIVE: Preconditioning the heart with 5 min of ischaemia followed by reperfusion renders the myocardium resistant to infarction from subsequent ischaemia. This protection lasts for about 1 h. The aim of this study was to test whether the protection could be reinstated with a second episode of preconditioning after protection from an initial episode had worn off. METHODS: To induce infarction animals experienced 30 min of coronary artery occlusion and then 3 h reperfusion. Ischaemic preconditioning was accomplished with 5 min of coronary branch occlusion. In one group of rabbits the subsequent reperfusion period was prolonged to 2 h to permit protection to wear off before the 30 min coronary occlusion was initiated. In another group a second 5 min coronary occlusion was performed at the end of the 2 h reperfusion. After 10 min of reperfusion the 30 min ischaemic period began. Control animals experienced only the 30 min ischaemia and 3 h reperfusion. Infarct volume was measured with tetrazolium and expressed as a percentage of the ischaemic zone volume. RESULTS: Average infarct size in seven control rabbits [36.0 (SEM 2.0)% of the ischaemic zone] was not significantly different from that in eight rabbits with the prolonged coronary occlusion occurring 2 h after the preconditioning stimulus [28.6 (2.9)% infarction]. In contrast infarcts were significantly smaller in the re-preconditioned group of seven rabbits [8.3 (4.2)%] and comparable to those previously seen with a single preconditioning stimulus followed 10 min later by the 30 min occlusion [6.1 (1.8)%]. CONCLUSIONS: The rabbit heart can be protected with a second preconditioning stimulus after protection from an initial period of preconditioning has subsided.

Animals↗
PubMed1993

Heparin does not stimulate coronary-collateral growth in a canine model of progressive coronary-artery narrowing and occlusion.

To investigate the possible effect of heparin on coronary-collateral growth, dogs were instrumented chronically with a left circumflex (LCF) flow probe, an ameroid constrictor, a balloon occluder, and left and right atrial and aortic catheters. Collateral blood flow was measured at least weekly or when the coronary artery was occluded. Animals were allocated randomly to a control or treatment group. The latter received a continuous right-atrial infusion of a heparin solution at a rate of 2 to 3 ml/hour and a concentration adjusted daily to increase the activated clotting time to approximately 3 times the pre-drug level. After LCF occlusion, coronary-collateral flow was measured during exercise. There was no difference in time to LCF occlusion in the anticoagulated dogs. Furthermore, neither the rate of collateral development, the magnitude of collateral flow shortly after spontaneous LCF occlusion, nor the degree of collateral vascular reserve during exercise was different in the two groups. Therefore, in this model of coronary obstructive disease, heparin does not accelerate coronary-collateral development.

Analysis of Variance↗
PubMed1993

Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction.

BACKGROUND: The vulnerability of the myocardium of a diabetic animal to an ischemic insult is controversial. To address this issue, streptozotocin-induced non-insulin-dependent diabetes (NIDD) was induced in rats, and the effects of regional myocardial ischemia were assessed by measuring infarct size. METHODS AND RESULTS: Open-chest rats with NIDD and age-matched control rats underwent 30 or 45 minutes of regional ischemia and 2-hour reperfusion. Infarct size was measured by tetrazolium. Control rats had 32.0 +/- 3.3% infarction of the risk zone after a 30-minute coronary occlusion, whereas NIDD rats had significantly smaller infarcts (11.5 +/- 3.1% of the risk area, P < .005). When ischemic time was extended to 45 minutes, infarct size in control animals averaged 57.9 +/- 6.2%, whereas only 37.3 +/- 5.6% of ischemic myocardium was infarcted in NIDD rats (P < .05). In a subset NIDD group, rats experienced a period of ischemic preconditioning (three cycles of 5-minute ischemia/5-minute reperfusion) before 45-minute ischemia. Infarct size in these rats averaged only 6.9 +/- 3.0% (P < .01 vs nonpreconditioned NIDD rats with 45-minute coronary occlusions). Collateral flow was measured in NIDD rat hearts with radioactive microspheres. Collateral flow was < 1% of normal myocardial blood flow. CONCLUSIONS: We conclude that NIDD protects the heart from infarction and that this protection is not related to the development of coronary collaterals. Furthermore, preconditioning can further protect the NIDD heart.

Animals↗
PubMed1993

Catecholamines can induce adenosine receptor-mediated protection of the myocardium but do not participate in ischemic preconditioning in the rabbit.

The role of catecholamines in ischemic preconditioning is unclear. Accordingly, the effects of tyramine-induced norepinephrine release and alpha 1-receptor blockade were examined. Ischemic preconditioning with a 5-minute coronary occlusion 10 minutes before a 30-minute ischemic interval resulted in only 7.7 +/- 3.1% infarction of the risk area, significantly less than that in control rabbits with isolated 30-minute coronary occlusions (34.4 +/- 3.2%, P < .01). Intravenous infusion of tyramine 10 minutes before 30 minutes of ischemia also protected the heart from infarction to an extent similar to that seen with ischemic preconditioning (6.9 +/- 2.4% infarction). This protection observed with tyramine infusion was eliminated by alpha 1-receptor blockade with BE 2254 (36.8 +/- 2.6% infarction) but was unaffected by beta-blockade with propranolol (10.5 +/- 2.4% infarction). Furthermore, the protection was unaffected when the tyramine-induced hypertension was attenuated by allowing blood to flow into a volume reservoir (3.9 +/- 0.8% infarction, P < .01 vs control value). The nonselective adenosine-receptor blocker PD 115,199 also eliminated tyramine-induced protection (40.2 +/- 5.6% infarction), indicating that adenosine is involved in adrenergic-mediated protection. BE 2254 could not block ischemic preconditioning (3.9 +/- 1.1% infarction, P < .01 vs control value). Therefore, catecholamine release before prolonged ischemia can protect the heart from infarction via the alpha 1-receptor, but adenosine receptor stimulation is also involved. alpha-Adrenergic stimulation does not appear to be critical to the protection observed after ischemic preconditioning.

Adenosine↗
PubMed1992

Adenosine is an endogenous protectant against stunning during repetitive ischemic episodes in the heart.

To investigate whether adenosine receptor blockade alters the response to serial coronary occlusions in the rabbit heart, we measured changes in segment length with ultrasonic dimension gauges placed in the field of a coronary branch. The coronary branch was subjected to four 5-minute occlusions, each separated by 10 minutes of reperfusion. In control hearts, the percentage of segment shortening fell from 15.7% to 9.3% after release of the first occlusion with no further deterioration after each of the subsequent three occlusions. In hearts in which adenosine receptors were blocked with PD 115,199, a potent blocker of both A1 and A2 receptors, segment shortening again recovered to about two thirds of the preischemic value during the reperfusion period after the first occlusion. Each subsequent occlusion, however, resulted in a further deterioration of function to the extent that shortening was less than 20% of the preischemic value during reperfusion after the fourth occlusion. Therefore the first occlusion of a series of four occlusions, while mildly stunning the heart, also preconditions the myocardium against further stunning by subsequent occlusions. Because that protection was when adenosine receptors were blocked, adenosine must play an important role in the mediation of this protective effect.

Adenosine↗