Progression of myocardial abnormalities in experimental alcoholism.
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Alcoholism↗
Biomedical subjects
B Haider
Publications and source records attributed to B Haider.
Cell sodium and the induction of myocardial injury after adrenaline.
Accumulation of calcium in cardiac cells during catecholamine induced injury is considered a major pathogenetic factor but its mechanism has not been defined. During initiation of injury in an intact canine model, cell sodium was enhanced fourfold in myocardium after a local infusion of epinephrine via the left anterior descending coronary artery for a 60 min period. Tissue calcium was enhanced and a major role for the Na-Ca carrier system is suggested. Regional myocardial function, blood flow and electrocardiogram responses to toxic levels of the catecholamine have been contrasted with ischaemic injury.
Animals↗
Dissociation of myocardial sodium and potassium alterations in mild versus severe ischemia.
To determine the relative influence of two levels of ischemia on myocardial cation and water composition as well as cardiac function, intact anesthetized dogs were studied for 1 h using a balloon-tip catheter in the proximal left anterior descending coronary artery. Hemodynamic studies in group A revealed a diminished ejection fraction during mild and severe ischemia associated, respectively, with a 36% and 74% decline in transmural coronary flow. Left ventricular end diastolic pressure rose only after severe ischemia. Greater accumulation of sodium and water and loss of K+ in ischemic tissue was observed in animals with severe ischemia. In group B, intracellular cations and water were estimated on the basis of 51Cr-labeled EDTA distribution. The extracellular space was unaltered at either level of ischemia. During mild ischemia, cell Na+ and H2O were enhanced in the inner and outer layers of myocardium. Despite a 25% reduction in subendocardial blood flow by the labeled microsphere technique, K+ content was normal. After severe ischemia, cell K+ was reduced in inner and outer layers. However, the increase of cell Na+ content substantially exceeded K+, suggesting a major effect on the sodium pump or cell permeability.
Animals↗
Relation of platelets to catecholamine induced myocardial injury.
To test the thesis that myocardial injury, induced by catecholamines, is ischaemic in origin due to platelet accumulation in the coronary microvasculature, sustained left intracoronary and systemic infusion of catecholamines in toxic dosage was given to dogs previously infused with autologous 51Cr-labelled platelets. Subsequent determination of tissue radioactivity and electrolytes, as well as electronmicrography, indicated that the induced myocardial injury was not related to microvascular occlusion by platelets.
Animals↗
Antiarrhythmic effects of aspirin during nonthrombotic coronary occlusion.
To study the action of aspirin upon the myocardium per se, independent of thrombosis, coronary occlusion with a balloon catheter was induced in 53 anesthetized dogs divided into two groups. One group (N = 20) was treated daily with aspirin (600 mg/dog) for seven days and another (N = 33) was untreated. Left ventricular hemodynamics and precordial ECG mapping were used to assess the influence of myocardial ischemia over a four hour period. There were no significant differences in left ventricular function or extent of injury as judged by ECG mapping between the two groups. However, there was a significant decrease in the incidence of ventricular fibrillation in the treated dogs (5% vs 39%). Serial plasma samples for free fatty acid determination showed a significant rise in the untreated group. Aspirin blocked the FFA increment in the treated animals. Tissue samples from the ischemic area of left ventricle exhibited a significant reduction of the sodium and water increments, as well as a lesser potassium loss in the treated animals compared to the controls and may have been the basis for the lower incidence of arrhythmias. Since infusion of 51Cr labelled platelets showed no myocardial accumulation of platelets in either group, microthrombi did not appear to contribute to the observed differences.
Animals↗
Altered myocardial function and collagen in diabetic rhesus monkeys on atherogenic diet.
We have demonstrated that in rhesus monkeys, 18 months of diabetes alters the end-diastolic pressure, end-diastolic volume relations without hypertrophy. Accumulation of collagen in the myocardial interstitium was the apparent basis for abnormal left ventricular performance. Neither collagen concentration nor left ventricular performance were signigicantly affected by dietary lipid composition. These myocardial abnormalities occurred at a stage when coronary atherosclerosis was limited. However, the relative influence of coronary atherosclerosis and myocardial alterations during more prolonged lipid feeding remains to be determined.
Animals↗
The myocardium and its vasculature in diabetes mellitus: Part II.
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Adult↗
Spontaneous heart rate, ventricular tachycardia, and the response to procainamide during acute ischemia.
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Animals↗
The role of ethanol in cardiac disease.
The widespread use of ethyl alcohol suggests its potential importance in clinical medicine. There is no proven therapeutic effect in cardiac patients and its role as an etiologic factor in heart disease has been disputed over the years and attributed to coexistent malnutrition. The latter factor, however, has been dissociated from ethanol use in many patients with the cardiomyopathic form of heart failure. Major support for the role of ethanol as a toxic agent when used in large amounts for a prolonged period has been obtained in various species of animals, including the subhuman primate. Abnormalities include depression of ventricular function, and metabolic and morphologic changes that parallel the changes in humans with preclinical malfunction of the heart. While the mechanism of progression to heart failure or arrhythmias is not known, several factors may be associated. These include, particularly in males, the cumulative effects of ethanol alone or after intensified drinking episodes, simultaneous exposure to trace metals in excess, and occasional specific nutritional deficiency or superimposed infection. The low prevalence of clinical nutritional deficiency in patients with alcoholic cardiomyopathy and the infrequency of heart disease in patients with cirrhosis or neuropathy supports the view that the cardiac abnormality is commonly not dependent on malnutrition. Clinical data indicate that the cessation of alcohol intake may reverse the disease or interrupt its progression in many patients. However, the pathogenic process may continue unabated in some patients who become abstinent.
Alcoholism↗
The effects of tolbutamide on the myocardium in experimental diabetes.
The effects of chronic tolbutamide treatment were examined in a diabetic animal model in which abnormal myocardial function and composition have previously been demonstrated. Eight diabetic dogs were given tolbutamide 250 mg/day orally and compared with seven untreated diabetics, five healthy dogs receiving tolbutamide, and eight normal controls. After one year, resting hemodynamic studies in the intact anesthetized state showed that treated diabetic dogs had a significantly higher left ventricular end-diastolic pressure of 12.1+/-1.3 mm Hg associated with normal end-diastolic volume, compared to 6.1+/-0.8 mm Hg in untreated diabetics (P less than 0.01) and 6.3+/-0.5 in normals. Stroke work and ejection fraction were similar to normals. Acute volume expansion revealed a larger rise of left ventricular end-diastolic pressure in treated and untreated diabetics than normals, without a significant stroke volume response in treated diabetics. Enhanced stiffness of myocardium appeared to be related to interstitial accumulation of periodic acid-Schiff staining material, further intensified in treated diabetics by triglyceride accumulation observed on electron microscopy and by chemical analysis. Thus treatment of diabetes with tolbutamide, despite improved glucose tolerance, effected further reduction of left ventricular function and altered morphology of myocardium.
Animals↗
Myocardial function and coronary blood flow response to acute ischemia in chronic canine diabetes.
To examine the influence of preexistent diabetes mellitus on left ventricular performance and coronary blood flow responses to acute ischemia, mild normoglycemic diabetes was induced in nine mongrel dogs after three doses of alloxan, (20 mg/kg, iv), at monthly intervals. Hemodynamic measurements and coronary blood flow (85Kr clearance) were obtained before and after the onset of ischemia. This was produced by occlusion of the proximal left anterior descending coronary artery via a balloon-type catheter in nine intact anesthetized diabetic dogs and 10 nondiabetic dogs. During the 1st hour of ischemia in the diabetic group, the end-diastolic pressure rose from 7 +/- 1.1 (mean +/- SE) mm Hg to 23.8 +/- 2.3 without a significant increase of end-diastolic volume. In controls end-diastolic pressure rose from 8.6 +/- 1.1 mm Hg to 15.3 +/- 1.4, and end-diastolic volume was significantly increased, so that the ratio of end-diastolic pressure and volume was significantly higher in the diabetic group (P less than 0.005). Although indices of contractility did not differ, stroke volume and work reductions were significantly greater in diabetics, despite the fact that coronary blood flow was reduced to a similar extent. Size of the ischemic areas appeared comparable as judged by distribution of dye injected distal to the occlusion. Since potassium loss and sodium gain in the inner and outer layers of ischemic tissue did not differ between the two groups, the intensity of ischemia seemed similar. Glycogenolysis was unimpaired in the diabetic ischemic muscle but triglyceride levels remained elevated. Morphologically the diabetic myocardium was characterized by a diffuse accumulation of periodic acid-Schiff-positive glycoprotein in the interstitium, which was thought to limit diastolic filling of the ischemic ventricle and to contribute to the substantial reduction of ventricular performance.
Animals↗
Evidence for cardiomyopathy in familial diabetes mellitus.
Recent epidemiologic studies have suggested that cardiac disease in common in diabetics and may often have a noncoronary basis. To examine the status of the left ventricle, 17 adult-onset diabetics of familial type without hypertension or obesity underwent hemodynamic study and were compared to 9 controls of similar age. Of the 17, 12 subjects had no significant occlusive lesions by coronary angiography. From this group eight without heart failure had a modest, but significant, elevation of left ventricular end-diastolic pressure. End-diastolic and stroke volumes were reduced, but ejection fraction and mean rate of fiber shortening were within normal limits. The left ventricular end-diastolic pressure/volume ratio was significantly higher than controls. Afterload increments effected a significant increase of filling pressure compared to normals without a stroke volume response, consistent with a preclinical cardiomyopathy. Four patients with prior heart failure had similar but more extensive abnormalities. None had local dyskinesia by angiography, and lactate production was not observed during pacing-induced tachycardia. Left ventricular biopsy in two patients without ventricular decompensation showed interstitial collagen deposition with relatively normal muscle cells. These findings suggest a myopathic process without ischemia. Postmortem studies were performed in 11 uncomplicated diabetics. Nine were without significant obstructive disease of the proximal coronary arteries, and the majority succumbed with cardiac failure. On left ventricular sections, none had evident luminal narrowing of the intramural vessels. All nine exhibited periodic acid-Schiff-positive material in the interstitium. Collagen accumulation was present in perivascular loci, between myofibers, or as replacement fibrosis. Multiple samples of left ventricle and septum revealed enhanced triglyceride and cholesterol concentrations, as compared to controls. Thus, a diffuse extravascular abnormality may be a basis for cardiomyopathic features in diabetes.
Adult↗
Myocardial ischemia and cell acidosis: Modification by alkali and the effects on ventricular function and cation composition.
Myocardial cell pH was measured with 5, 5 dimethyl-2, 4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular and water indicators were made into the left anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady state distribution of DMO between cells and plasma was calculated from the mean transit times of the indicator. Normal myocardial cell pH averaged 6.94 and changed by 58% of the concomitant alterations in plasma pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a balloon tip catheter in the left anterior descending coronary artery resulted in progressive decreases in cell pH to 6.59 by 1 hour. Infusions of sodium carbonate diminished intracellular acidosis. Hemodynamic studies during 4 hours of ischemia with blood pH at 7.55 to 7.60 indicated a significantly reduced left ventricular end-diastolic pressure and increased stroke volume by comparison with findings in animals given infusions of saline solution. Ventriculograms revealed improved wall motion in the ischemic segment after infusion of alkali. Precordial mapping showed a significant reduction in the number of leads with S-T segment elevation as well as in the sum of S-T segment elevations, but R wave amplitudes did not differ from those in control studies. Calculations of extracellular space, tissue water and cation content revealed a reduced gain of cell sodium ion and loss of cell potassium ion during ischemia after alkali treatment. The latter may account for the S-T segment responses, whereas enhanced ventricular performance may be related to reduced competition of hydrogen ion with calcium ion for binding sites on contractile protein.
Acidosis↗
Evaluation of potassium-43 scintillation images during early myocardial ischemia in an animal model.
To assess the validity of myocardial imaging with potassium-43 (43K) early after the onset of ischemia, the left anterior descending artery was occluded with a baloon tip catheter in 32 intact anesthetized dogs. 99mTechnetium ventriculograms localized the left ventricle. 43K was administered intravenously and serial images were obtained in four views using an Anger camera with a pinhole collimator. The heart was arrested after 60 minutes and removed for imaging and tissue counts to ascertain extracardiac and geometric factors. In normals (group 1) left ventricular images were relatively homogeneous, except for the thin walled apex, both in vivo and in the isolated heart. Equilibration with 43K prior to ischemia (group 2) gave similar images to group 1, associated with a small reduction in tissue count after one hour of ischemia. Group 3 was infused with 43K after initiation of ischemia. Despite a reduction of 43K counts in the ischemic area to less than one-fourth of the nonischemic site (P less than 0.001), demonstration of a "cold area" in vivo was inconstant, occurring in only 34% of studies. Lead shielding did not improve accuracy. In the isolated heart the ability to detect the cold area was improved to 73%. However, when the left ventricle was incised and spread flat, so that low and high activity areas were contiguous rather than superimposed, a widespread area of ischemia was present without exception in the anterior wall. Use of a rectilinear scanner in seven animals failed to improve diagnostic yield; areas of reduced radioactivity were seen at the apex in normals by both techniques. Thus, while detection of low flow areas in the isolated heart is feasible by isotopic imaging early after the onset of ischemia, both extracardiac and geometric factors can contribute to qualitative and quantitative errors in vivo.
Animals↗
Effect of coronary thrombus age on fibrinogen uptake.
A study was carried out to define the time limits during which an experimental coronary thrombus remains capable of incorporating fibrinogen. 131I-fibrinogen was given to intact anesthetized dogs at different time intervals, up to 67 hours, following the formation of a coronary thrombus by catheter-electrode. Radioactivity of the recovered thrombi as a whole and segmentally divided, was determined following variable time intervals of exposure to circulating fibrinogen and was expressed as thrombus/blood ratio. The results indicate that coronary thrombi formed in a normal coronary vessel remain capable of incorporating fibrinogen for at least eighteen hours, with no significant differences in the segmental distribution of radioactivity. These findings do not support the view that the recovery of isotopic fibrinogen, which was given after the onset of coronary symptoms, in thrombi from patients with myocardial infarction establishes that the thrombus was initiated after the ischemic process.
Animals↗
Heart cell responses to ethanol.
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Alcoholism↗
Ischemic heart failure: sustained inotropic response to small doses of I-epinephrine without toxicity.
As a prelude to a study of severe ischemic heart failure, the therapeutic response of the ischemic ventricle to epinephrine and acetylstrophanthidin in nontoxic doses was determined in 24 intact anesthetized dogs undergoing a first episode of acute regional ischemia. A thrombotic obstruction was produced in the left ventricular dysfunction. The elevation of end-diastolic pressure and reduced stroke volume in control dogs were not significantly altered by administration of strophanthidin. Epinephrine (0.05 mug/kg per min) elicited a significant reduction in end-diastolic pressure and increase in stroke volume. The latter was not attended by an increased incidence of ventricular fibrillation, whereas fibrillation occurred in half of the group given strophantihidin. Thus, the catecholamine was selected to study pump failure. Severe ischemic heart failure was assessed in two groups with scar from previous infarction for up to 4 hours. By 60 minutes of ischemia the increase in end-diastolic pressure and volume and decrease in stroke volume and ejection fraction were comparable in both groups. Thereafter, alternate animals received small doses of epinephrine (0.05 to 0.15 mug/kg per min) with graded increments at 60 minute intervals to counter tachyphylaxis and findings were compared with those in control dogs. Over the subsequent 3 hours, there was progressive deterioration of left anterior descending coronary artery, affecting ventricular function in the untreated group with an increase in end-diastolic pressure from 10 plus or minus 1 to 33 plus or minus 2.4 mm Hg. End-diastolic volume increased by 63 percent; stroke volume and ejection fraction decreased by 48 and 66 percent, respectively. The infusion of epinephrine was attended by a significantly lower end-diastolic pressure of 20 plus or minus 2.5 mm Hg, whereas end-diastolic volume, stroke volume and ejection fraction were restored to control levels after 4 hours of ischemia. Mortality in the untreated group was 62 percent by 4 hours; all seven animals in the treated group survived.
Animals↗
In vivo myocardial cell pH in the dog. Response to ischemia and infusion of alkali.
Myocardial cell pH has been measured with 5,5-dimethyl-2,4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular, and water indicators were made into the anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady-state distribution of DMO between cells and plasma was calculated from the indicator mean transit times, and the plasma pH. Myocardial cell pH was determined from the distribution value and plasma pH. Normal myocardial cell pH averaged 6.94. Changes in myocardial cell pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a coronary artery balloon resulted in progressive decreases in cellular pH to average values of 6.83 within the initial 15 min and to 6.59 within the interval between 20 and 70 min. Infusions of Na2CO3 tended to diminish intracellular acidosis although these infusions had little effect on the difference in pH between the myocardial cell and extracellular fluid.
Acid-Base Equilibrium↗