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Biomedical subjects

T J Regan

Publications and source records attributed to T J Regan.

At least 55 records · Page 3Linked to original sources
PubMed1982

Effects of oxygen administration and alteration in arterial PCO2 on ischemic myocardial changes following experimental coronary artery ligation.

In acute myocardial infarction the effect of oxygen administration in modifying infarct size is uncertain. To evaluate this as well as the effects of moderate hypocarbia, four groups of anesthetized dogs were studied experimentally for 2 hours after coronary branch ligation: group I (controls; room air, normal blood gases): group IIA (FIo2 50%, normal Paco2); group IIB (FIo2 50%, low Paco2); and group IIC (50% oxygen given after ligation, normal Paco2). In addition to hemodynamics, the effect of differing blood gas patterns on hemoglobin-oxygen affinity (P50) and ischemic alterations of myocardial electrolyte and water content were evaluated. Hemodynamic changes among the four groups included decreases in LV ejection fraction and cardiac output. The latter was more pronounced in the oxygen treated groups with proportionately greater increases in systemic resistance. P50 increased in all groups, indicating decreased hemoglobin-oxygen affinity; in group IIC this increase was significantly greater than in group I. In all groups an analysis of central and border areas of myocardial ischemia showed loss of potassium and gain of sodium and water, but no beneficial effect on this result by oxygen administration pre or post ligation could be demonstrated. On the contrary, among those dogs administered oxygen the ischemic changes appeared more pronounced than in the control group. Moderate hypocarbia did not modify the myocardial electrolyte and water change. The results of this study do not support the hypothesis that oxygen administration can favorably modify the myocardial changes of ischemia, at least early in the course of myocardial infarction.

Animals↗
PubMed1982

Cardiovascular complications.

This report summarizes the current state of knowledge concerning the cardiovascular system in various animal models of diabetes and presents their major strengths and weaknesses for studying the important research questions in the field. Nonhuman primates have many desirable features for studies on the macrovascular and cardiac complications of the disease as well as risk factor alterations, but their availability, cost, and maintenance present practical disadvantages. The spontaneous rodent models of diabetes currently are not considered very useful for cardiovascular research, but they have not been well characterized with respect to most aspects of their cardiovascular system. Alloxan-diabetic rabbits offer some promise for examining the effects of diabetes on atherogenesis, lipoprotein metabolism, and cardiomyopathy, but additional research is required to validate their usefulness. Insufficient data are available on canine and swine models of diabetes to judge their merits for cardiovascular research. The Task Force recommends: (1) additional longterm investigations to determine the extent and severity of cardiovascular complications in the well-characterized rodent models and in diabetic rodents with multiple risk factor abnormalities; (2) further studies on the macrovascular disease and lipoprotein abnormalities of the alloxan-diabetic rabbit and the development of rabbit colonies with spontaneous diabetes; (3) increased emphasis on such potentially important but neglected areas of research in diabetic animals as the intramyocardial circulation, adventitial blood vessels, blood pressure, platelet function, blood coagulation, blood rheology, and autonomic nervous function; (4) long-term studies on the influence of control of hyperglycemia and of insulin therapy on cardiovascular complications in diabetic animals; and (5) encouragement of use of diabetic nonhuman primates for cardiovascular research and institution of measures to increase their supply and availability by expanding current colonies, screening newly imported animals for diabetes, and establishing a visiting scientist's program allowing investigators to study diabetic primates at resource centers.

Animals↗
PubMed1982

Regional circulatory responses to alcohol and its congeners.

The circulatory responses to ethyl alcohol are quantitatively related to the route and rate of administration as well as to the dose and the time of physiological measurements. A variety of acute regional blood flow responses have been described in the basal state in animals without prior exposure to ethanol. Gastric mucosal blood flow is substantially increased by ethanol. Pancreatic blood flow, on the other hand, has been found to undergo a dose-dependent reduction. Hepatic blood flow has been found to increase in baboons without evidence of ischemia. Renal arteries appear to be unresponsive up to 3 g/kg. Similarly, the cerebral vasculature does not seem to be affected by ethanol except at high dose levels where increased flow occurs. Animal studies, however, have suggested that ethanol may interfere with autoregulation. In terms of limb blood flow, oral administration has been found to enhance flow to the skin but to diminish skeletal muscle blood flow. Vasodilatation of the coronary vasculature has been consistently reported to be significantly greater in animals than in humans. The major metabolite of ethanol, acetaldehyde, has significant effects on circulation. At blood levels achieved after feeding ethanol, there was a 60% rise of coronary blood flow but myocardial oxygen consumption was reduced, presumably representing a shunting effect in myocardium.

Acetaldehyde↗
PubMed1981

Evaluation of thallium-201 imaging in nontransmural ischemia and infarction.

To assess the validity of thallium-201 myocardial imaging in the diagnosis of nontransmural ischemia and infarction, the proximal left anterior descending coronary artery was partially occluded for 60 minutes with a balloon-tip catheter in intact anesthetized dogs in a basal state or during atrial pacing. In vivo scintigrams of myocardium were compared with those obtained in the isolated heart and in the incised ventricle spread flat. None of the animals with partial occlusion with or without pacing demonstrated abnormal scintiscans in vivo. Removal of background by isolating the heart increased positive images to 30%; positive images were associated with an isotope count ratio between ischemic and normal muscle of less than 0.67. Removal of superimposed nonischemic muscle in the heart enface increased image detection after pacing to 11 of 15. Since animals with subendocardial scar failed to demonstrate a "cold area" in vivo, unfavorable geometry as well as extent and degree of ischemia appear to be important. Thus, thallium radioactivity in superimposed and adjacent myocardium, as well as background, may limit the detection of nontransmural ischemia and scar.

Animals↗
PubMed1981

Assessment of left ventricular contractile performance from isovolumic relaxation phase in man.

The rate of left ventricular (LV) pressure fall (dP/dtmin) is reportedly altered by contractility and LV stress. To explore the possibility that the ratio of dP/dtmin to dicrotic notch pressure (DTES) measures contractility, 243 subjects including 23 normals (group I) were studied. In 35 patients of group II (16 with mitral stenosis, 7 with atrial septal defect, and 12 with cor pulmonale) DTES, as an index of contractility (Cy Ix) measuring force-velocity-length relationship, was insignificantly different from group I (DTES and Cy Ix in group I = 21.6 +/- 0.6 s-1 and 1.34 +/- 0.04 muscle lengths/s/cm and 18.8 +/- 1.8 s-1 and 1.55 +/- 0.24 muscle lengths/s/cm in group II, respectively). With significantly reduced Cy Ix (1.05 +/- 0.04, p less than 0.01), DTES was likewise reduced (19.0 +/- 0.5, p less than 0.01) in 163 patients with compensated LV disease (47 with alcoholic cardiomyopathy, 24 coronary artery disease, 48 valve disease, 10 hypertensives and 34 with other heart muscle diseases). Like the Cy Ix (0.70 +/- 0.05, p less than 0.001), DTES was even lower (13.3 +/- 0.6, p less than 0.001) in 15 patients with decompensated LV (group IV). Like Cy Ix, this ratio changed significantly with acute changes in inotropy (exercise and pacing), but not with preload (dextran infusion). Basal heart rate, preload and afterload did not influence DTES. Furthermore, DTES correlated significantly in all groups and subgroups with two indices of contractility, VCE (velocity of contractile element) at peak isometric stress, and Cy Ix (r = 0.68 and 0.70, respectively, each p less than 0.001) measured in this study. These results indicate that DTES provides a simple, reliable, and useful measure of the contractile state of LV myocardium in man, independent of preload and afterload.

Cardiomyopathies↗
PubMed1981

Effect of sulfinpyrazone on ventricular fibrillation during acute myocardial ischemia.

In patients treated with sulfinpyrazone, an apparent reduction in the incidence of sudden death and presumed ventricular fibrillation has been reported. Using an intact animal model without microcirculatory thrombosis, we studied the effects of sulfinpyrazone on ischemic myocardium in 58 anesthetized dogs divided into three groups: control untreated (n =24), group 1 (n = 16), treated daily with 300 mg of sulfinpyrazone for 7 days, and group 2 (n = 18), treated daily with 300 mg of sulfinpyrazone for 7 days but omitting treatment on day 8. Although consistent hemodynamic differences were not apparent, the degree of injury determined by ECG mapping was significantly lower in group 1. The incidence of fibrillation was 54% for control and 0% in group 1. Group 2 had a 44% incidence, suggesting a limited duration of action. The apparent absence of microcirculatory thrombosis in this model suggests other mechanisms of action. A significantly smaller increase in tissue water and Na+ and smaller loss of K+ in group 1 may have contributed to the lower incidence of fibrillation, perhaps through selective prostaglandin inhibition.

Acute Disease↗
PubMed1981

Myocardial composition and function in diabetes. The effects of chronic insulin use.

This study was undertaken in an animal model of mild diabetes to determine if provision of chronic insulin replacement during postprandial hyperglycemia may modify the abnormalities of myocardium. Group 1 served as controls with normal glucose tolerance by intravenous testing. Two additional groups were made diabetic with low doses of alloxan. Diabetic animals of Group 2 were untreated (n = 6). Group 3 animals (n = 6) received regular insulin daily to reduce postprandial hyperglycemia. After one year with maintained body weight, the animals were studied in the intact anesthetized state using the indicator dilution technique for left ventricular volume determinations. Basal left ventricular function and contractility were similar to normals in both diabetic groups. During intraventricular infusion of saline, end-diastolic pressure rose to higher levels in untreated diabetes (14.8 +/- 2 mm Hg) than normals (8.8 +/- 0.84), despite similar basal levels. Insulin treatment was associated with higher filling pressures than in group 1 as well as reduced end-diastolic volume response. Collagen concentrations were enhanced an average of 50% in layers from the inner to outer myocardium in both untreated and treated diabetics, associated with sodium and water accumulation. Since hypertrophy was not present, the diminished compliance appeared related to increased collagen levels. On electron microscopy, the subcellular organelles of the cardiac cell appeared normal in both diabetic groups. Thus, collagen accumulation and abnormal myocardial function in this model of diabetes is not affected by control of postprandial hyperglycemia, but a potential role for sustained hormone replacement is not excluded.

Animals↗
PubMed1981

Ethanol abuse and heart disease.

The toxic effects of chronic ethanol abuse on cerebral and hepatic function have long been recognized. The role of ethanol abuse as an etiologic factor in heart disease is less clear and is often attributed to coexistent malnutrition. However, malnutrition has been dissociated from ethanol use in many patients with congestive cardiomyopathy. Studies in various animals provide major support for the role of ethanol as a toxic agent when used in large amounts for a prolonged period. Abnormalities that result from ethanol in test animals include depression of left ventricular performance and metabolic and morphologic changes that parallel the changes in human alcoholics with subclinical mechanical dysfunction of the heart, such as symptomatic cardiac arrhythmias, particularly during intensive alcohol ingestion. What causes the progression to heart failure or arrhythmias is not known, but several factors may be involved. These include, particularly in males, the cumulative effects of ethanol alone or after intensified drinking episodes, excessive exposure to trace metals or superimposed infection. The low prevalence of clinical nutritional deficiency in patients with alcoholic cardiomyopathy and the apparent infrequency of heart failure in patients with cirrhosis or neuropathy supports the view that the cardiac abnormality is often 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 pathogenetic process may continued unabated in some who become abstinent.

Alcoholism↗
PubMed1981

Depression of myocardial function during acute pancreatitis.

The left ventricular function of 24 patients with acute pancreatitis was studied noninvasively using systolic time intervals. Seven of the 24 patients were reevaluated 4-40 days following the onset of acute symptoms. During the acute phase the PEP/LVET ratio was significantly prolonged to 0.470 +/- 0.031 and later declined to 0.376 +/- 0.017 (P less than 0.01). The convalescent value is similar to the low grade abnormality found in noncardiac alcoholics without pancreatitis (0.381 vs 0.312 in age-matched normals). Since serum electrolytes were normal, serum cardiac isoenzymes were not elevated and there was no evidence of volume depletion in the initial stages, the transient cardiac depression produced by acute pancreatitis may be mediated by the postulated myocardial depressant factor from the pancreas.

Acute Disease↗
PubMed1980

Ventricular tachyarrhythmias in regional myocardial hyperkalemia: efficacy of three antiarrhythmic agents.

Potassium chloride infusion into the left anterior descending coronary artery induces a sequence of events analogous to those occurring during acute transmural ischemia. These include ST elevation, intramural conduction delay, ventricular techyarrhythmias and fibrillation. The influence of antiarrhythmic agents in an intact anesthetized canine model have not previously been tested. We have evaluated the efficacy of lidocaine, procaine amide and practolol in animals during regional hyperkalemia. In the untreated, only 9% survided a 20 minute observation period. All three treatment groups exhibited a reduced incidence of tachycardia and 74% survived the test period. In each treatment group this was associated with a further prolongation of intramural conduction time in the affected wall. This antiarrhythmic efficacy, thought possibly to be due to transformation of unidirectional to bidirectional block, supports the view that modulation of transcellular potassium activity contributes to the control of ischemic arrhythmias.

Animals↗
PubMed1980

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↗
PubMed1980

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↗