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Biomedical subjects

S M Krause

Publications and source records attributed to S M Krause.

25 records · Page 2Linked to original sources
PubMed1981

Augmented venous return: a model of left ventricular afterload reduction during the course of endotoxin shock.

Utilizing a canine model of endotoxin shock (E coli, 4 mg/kg, B6:026) the major determinants of cardiac output (preload, afterload, contractility, and heart rate) were simultaneously followed for 5 hr in four study groups: Group I: time-matched controls, Group II: endotoxin shock, Group III: endotoxin shock and femoral-femoral A-V shunt, and Group IV: A-V shunt control. Groups II and III demonstrated an initial, abrupt increase in total peripheral resistance (TPR), coronary vascular resistance (CVR), and pulmonary vascular resistance (PVR), and a decrease in cardiac output (CO), coronary flow (CF) and heart rate (HR) and stroke work (P less than 0.05). Group II then demonstrated a decrease in TPR, CVR, PVR with an increase in CO and CF but systemic arterial pressure did not return to control values. At approximately 3 hr, Group II developed a progressive increase in TPR, CVR, and PVR, and a decrease in CO, CF, and SW. Heart rate did not change. In contrast, at 3 hr Group III demonstrated no significant increase in TPR, CVR, or PVR, a progressive increase of CO and CF, and preservation of SW. It is hypothesized that endotoxin shock is characterized by an initial phase characterized by an increase in resistance and decrease in flow that is not affected by an augmented venous return. However, in the intermediate and latter stages of shock, there is a progressive increase in resistance and decrease in flow, increasing impedance to left ventricular ejection that results in an imbalance between myocardial oxygen supply and demand, contributing to the observed myocardial failure. An augmented venous return, by decreasing resistance (afterload) and increasing venous return (preload) preserves cardiac output and myocardial function and thus serves as a model of left ventricular afterload reduction during the course of endotoxin shock.

Animals↗
PubMed1980

Myocardial failure and excitation--contraction uncoupling in canine endotoxin shock: role of histamine and the sarcoplasmic reticulum.

Subendocardial and subepicardial sarcoplasmic reticulum (SR) were isolated from five groups of dogs following five hours of hemodynamic monitoring: Group 1, 6-8 mg/kg diphenhydramine (n = 5); Group 2, 0.5 mg/kg histamine phosphate, IV bolus; Group 3, 4.0 mg/kg Escherichia coli endotoxin (n = 5); Group 4, 6-8 mg/kg diphenhydramine, followed by 4.0 mg/kg E coli endotoxin (n = 5); and Group 5, time-matched, sham-operated controls (n = 5). The velocity of calcium uptake and ATP hydrolysis and the integrity of the transport system were determined (coupling ratio = mumoles Ca++/mumoles Pi). Control SR calcium-uptake velocities averaged 1.13 +/- 0.3 mumoles Ca++/mg-min, with no significant difference between the endocardium and epicardium. SR calcium uptake from the endotoxin shock group averaged 0.64 +/- 0.06 (endocardium) and 0.56 +/- 0.05 (epicardium) mumoles Ca++/mg-min (P < 0.01 from control).ATPase activity from the control group = 1.23 +/- 0.04 mumoles Pi/mg-min; and the endotoxin-shocked group exhibited an activity of 0.99 +/- 0.06, with no significant difference between the endocardial and epicardial populations (P > 0.1). Diphenhydramine-control SR calcium-uptake rates averaged 1.12 +/- 0.6 mumoles Ca++/mg-min, with no difference between endocardium and epicardium. Diphenhydramine pretreatment plus endotoxin-shock epicardial SR calcium uptake = 0.94 +/- 0.08 mumoles Ca++/mg-min, while the endocardial SR was significantly depressed at 0.72 +/- 0.04 mumoles Pi/mg-min, with no difference between endocardium and epicardium. Bolus histamine infusion resulted in a small but significant depression of both SR calcium-uptake rates (0.93 +/- 0.04 mumoles Ca++/mg-min) and ATPase activity (0.93 +/- 0.04 mumoles Pi/mg-min), with no significant difference between epicardium and endocardium. This study confirms that the calcium transport system of cardiac sarcoplasmic reticulum isolated from endotoxin-shocked animals is depressed. However, this depression is not due entirely to a depression of the Mg++-dependent, Ca++-stimulated ATPase enzyme, but is also associated with a significant uncoupling of ATP hydrolysis from calcium transport. The histamine blocker, diphenhydramine, was only able to protect the epicardial SR; the endocardial SR still exhibited an uncoupling of ATP hydrolysis from calcium transport. Bolus histamine infusion produced a small but significant depression of both calcium transport and ATP hydrolysis. These results are formulate d into a "proton-lysosome" hypothesis that appears to be able to explain excitation-contraction uncoupling in the endotoxin-shocked myocardium.

Animals↗
PubMed1980

Cardiogenic endotoxin shock: coronary flow and contractile protein dysfunction as determinants of depressed cardiac contractility.

Cardiogenic endotoxin shock (ES) refers to the intermediate and latter stages of ES characterized by a progressive myocardial dysfunction. This laboratory has been developing the hypothesis that a major etiology of this observed myocardial failure is a progressive state of global ischemia. In order to further test this hypothesis, ES (E coli, Difco Labs, 026:B6, 4 mg/kg) was induced in the canine model (n = 6) and coronary flow, myocardial contractility (dP/dtmax), and systemic hemodynamics were continuously monitored for five hours, following which the cardiac contractile proteins were isolated and characterized. In the ES group, control coronary flow (CF) = 90.5 +/- 3.6 ml/min/100 gm LV, coronary vascular resistance (CVR) = 61.82 X 10(3) +/- 2.28 X 10(3) dyne . sec. cm--5 and dP/dtmax 2,200 +/- 160 mm Hg/sec. Between four and five hours, CF decreased to 58.6 +/- 16 ml/min/100 gm LV, CVR increased to 128.6 X 10(3) +/- 18 X 10(3) dyne . sec. cm--5, and dP/dtmax decreased to 968 +/- 62 mm Hg/sec. Sham animals (n = 7) demonstrated no significant difference in CF, CVR, or dP/dtmax. Control myofibrillar ATPase activity demonstrated 50% activation (specific activity = 0.072 +/- 0.002 mumoles Pi/mg protein . min) at p Ca++ = 6.4, with no significant difference between endocardium and epicardium. ES myofibrils demonstrated 50% activation (specific activity = 0.060 +/- 0.002 mumoles Pi/mg protein . min endocardial, and 0.068 +/- 0.005 mumoles Pi/mg protein . min epicardial at pCa++ = 6.48 and 6.45, respectively, incriminating a change in affinity for Ca++ binding to the regulatory proteins. Thus, it would appear that the documented decrease in myocardial contractility is due in part to a depression of myofibrillar ATPase activity, which is related to a decrease in coronary flow, an increase in coronary vascular resistance, and a state of global myocardial ischemia.

Adenosine Triphosphatases↗
PubMed1980

Differential subendocardial perfusion and injury during the course of gram-negative endotoxemia.

This laboratory has been investigating the concept that a progressive state of global myocardial ischemia is a major precipitating factor in the etiology of the myocardial failure in endotoxin shock. To further test this hypothesis, endotoxin shock (E coli, B5, 4 mg/kg) was induced in the canine model, and coronary and systemic hemodynamics were monitored for five hours. Coronary flow decreased from 90.05 +/- 28 ml/min/100 gm left ventricle (n = 7) to 45 +/- 10 at five hours (n = 6), with two experimental deaths between four and five hours. Coronary vascular resistance increased from 61.82 +/- 2.5 X 10(3) dynes . sec . cm-5 to 128.6 X 10(3) +/- 18 X 10(3) dynes . sec . cm-5. Sham controls (n = 7) demonstrated no significant difference in either flow or resistance between zero to five hours. Gross examination of the shocked hearts demonstrated patchy to diffuse subendocardial hemorrhage not present in the sham preparations. Thioflavin S injection (4%, 1 ml/kg) demonstrated uniform perfusion under UV light (360 nm) in the sham preparations and marked nonuniform perfusion in the subendocardial surface of the shocked hearts. Histologic examination demonstrated diffuse intramyocardial hemorrhage, more marked in the subendocardium than the midmyocardium. Electron micrographs demonstrated swelling and distortion of the subendocardial sarcoplasmic reticulum and T-tubules and dehiscence of the myofibrils. It is concluded that the decrease in flow and concomitant increase in intramyocardial resistance progresses to a state of global ischemia and ischemic necrosis at the more vulnerable subendocardial surface.

Animals↗
PubMed1979

Diphenhydramine protection of the failing myocardium during gram-negative endotoxemia.

Gram-negative endotoxin (Escherichia coli, 4 mg/kg) was found to produce a sustained fall in systemic arterial pressure, left ventricular pressure, and cardiac output that could be blocked by the histamine antagonist diphenhydramine. Histamine infusion was found to produce a parallel depression of systemic arterial pressure. Further, endotoxemia was found to produce a significant depression of myocardial contractility (dP/dt max) that could also be blocked by diphenhydramine. Cardiac myofibrillar adenosine triphosphatase (ATPase) activity from endotoxin-shocked hearts was found to be depressed, ATPase activity from subendocardial myofibrils being more depressed than that from subepicardial myofibrils. Myofibrillar ATPase activity was significantly protected by pretreating the animals with diphenhydramine. It is concluded that the initial hemodynamic phase of endotoxin shock is histamine-mediated and that this hemodynamic depression can be blocked with diphenhydramine. Further, it appears that endotoxin is capable of depressing myocardial contractility by depressing contractile protein function (myofibrillar ATPase activity)--the subendocardial surface more so than the subepicardial surface--and this depression of myocardial contractility can be blocked with diphenhydramine.

Adenosine Triphosphatases↗