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M L Hess

Publications and source records attributed to M L Hess.

At least 109 records · Page 6Linked to original sources
PubMed1983

Calcium entry blockers: potential applications in shock.

Failure of the myocardium and vascular smooth muscle to maintain intracellular calcium homeostasis results in intracellular calcium overload leading in turn to cell death and tissue necrosis. This phenomenon can occur in myocardium in response to such diverse etiologies as catecholamine-induced necrosis, prolonged periods of hypoxia, low-flow states, and reperfusion of a previously ischemic vascular bed. Such conditions exist in the shock syndrome with its various etiologies. Cardiogenic shock is associated with primary myocardial failure and a low-flow state. The later stages of septic and endotoxin shock are associated with increasing peripheral vascular resistance and decreasing cardiac output. Experimental and clinical hemorrhagic shock are both associated with prolonged periods of low flow, and then with subsequent transfusion, reperfusion of previously ischemic vascular beds occurs. Therefore, in the shock syndrome, at least the potential for intracellular calcium overload exists. It is the purpose of this communication to discuss the pathophysiologic sequence of the shock syndrome, to illustrate the potential role of intracellular calcium overload in the progression of shock, to present a data base of the use of slow calcium channel blockers in the study of shock, and to suggest a future study of calcium entry blockers as potential therapeutic agents in the shock syndrome.

Animals↗
PubMed1983

Interaction of oxygen free radicals and cardiac sarcoplasmic reticulum: proposed role in the pathogenesis of endotoxin shock.

An initial event in gram-negative bacteremia is activation of the complement cascade with production of C5a. C5a, in turn, acts as a chemotactic stimulus for leukocytic aggregation and, in conjunction with bacterial products, stimulates the release of oxygen free radicals from leukocytes. We have hypothesized that these oxygen free radicals (.O2-, superoxide anion; .OH, hydroxyl radical; H2O2, hydrogen peroxide) contribute to the characteristic myocardial dysfunction of endotoxin shock, Isolated canine cardiac sarcoplasmic reticulum (SR) was used as a subcellular determinant of mechanical function. SR was incubated for 20 min at 37 degrees C in the presence of phorbol myristate acetate activated leukocytes (A-L) and calcium uptake and Ca2+-adenosine triphosphatase (ATPase) activities were measured. Activated leukocytes significantly depressed SR Ca2+ uptake rates (C = 1.12 +/- 0.05 mumol CA2+/mg-min; A-L = 0.73 +/- 0.05). The addition of catalase (CAT; 10 micrograms/ml) or superoxide dismutase (SOD: 10 micrograms/ml) plus CAT reversed the inhibition of SR Ca2+ uptake. SOD further depressed SR Ca2+ uptake (+SOD = 0.55 +/0 0.04 mumol Ca2+/mg-min). Mannitol had no effect. SR ATPase activity was inhibited with A-L (C = 1.41 +/- 0.04 mumol Pi/mg-min; A-L = 0.84 +/- 0.09). Neither mannitol, nor SOD nor CAT alone had any effect on the depression of SR ATPase activity. SOD plus CAT reversed the ATPase depression induced by A-L. It is concluded that phorbol myristate acetate activated leukocytes via free radical-mediated mechanisms can directly affect function and activity of the excitation-contraction coupling system of cardiac muscle. Free radical scavengers identified hydrogen peroxide as a major mediator of depressed Ca2+ uptake rates. In conjunction with the superoxide anion, hydrogen peroxide contributes to the depressed ATPase activity.

Animals↗
PubMed1983

Inhibition of surgically induced ischemia/reperfusion injury by oxygen free radical scavengers.

Recent experimental work implicates oxygen free radicals as mediators of ischemia/reperfusion injury. A simple cardioplegic solution was designed to scavenge superoxide anion and hydroxyl free radical with superoxide dismutase (10 micrograms/ml), mannitol (325 mOsm/L), and KCl 25 mEq/L (FRS). Hemodynamic and subcellular functions were studied in seven in situ canine models of hypothermic global ischemia receiving FRS, compared to a group (n = 7) receiving hyperosmolar, hyperkalemic saline (HSK) and to a standard model of topical hypothermia (TH, n = 5). Following 60 minutes of ischemia (10 degrees to 15 degrees C), hearts were reperfused and rewarmed. After 45 minutes of reperfusion, left ventricular peak systolic pressure (LVPSP), developed pressure (LVDP), dP/dt max, -dP/dt max, compliance, and elastic stiffness constant (K) were improved in the FRS group and not significantly different from control. Sarcoplasmic reticulum (SR) calcium transport in the FRS group was significantly improved (control = 1.077 +/- 0.022, TH = 0.754 +/- 0.018, HSK = 0.725 +/- 0.05, and FRS = 0.966 +/- 0.05 mumol/mg-min). Calcium adenosine triphosphatase (ATPase) activity did not differ significantly from control at pH 7.0. In this model of hypothermic global ischemia and reperfusion, free radical scavengers provide significant protection of mechanical and subcellular function. These findings support the hypothesis that oxygen free radicals are important mediators of myocardial ischemia and reperfusion injury.

Animals↗
PubMed1982

Influence of ATP on sarcoplasmic reticulum function of vascular smooth muscle.

A vesicular fraction isolated from bovine aorta and enriched in fragmented sarcoplasmic reticulum (FSR) exhibited active calcium transport and ATPase activity. By use of a hypotonic NaHCO3 extraction solution, an active preparation was isolated that retained activity for up to 4 days. A small but significant (P less than 0.05) Ca2+-stimulated, Mg2+-dependent ATPase associated with calcium transport was demonstrated with a specific activity of 0.33 mumol inorganic phosphate (Pi).mg-1.min-1. The basal Mg2+ ATPase demonstrated Michaelis-Menten kinetics [Km(Mg2+-ATP) = 0.44 +/- 0.01 X 10(-3) M; Vmax = 2.22 +/- 0.01 mumolPi.mg-1.min-1]. The Ca2+-stimulated, Mg2+-ATPase demonstrated apparent substrate inhibition (Ks approximately 10 mM) with no evidence for end-product (ADP) or excess added Ca2+ contributing to this inhibition. Oxalate-supported active calcium uptake velocities also exhibited quantitatively similar substrate inhibition. These results suggest that FSR from vascular smooth muscle contains either two enzymes or one enzyme with two isomeric forms, one of which is associated with the calcium uptake activity of this structure and the other of unknown function.

Animals↗
PubMed1982

Prevalence and significance of arrhythmias in long-term survivors of cardiac transplantation.

The prevalence and significance of arrhythmias after cardiac transplantation were evaluated in the absence of acute rejection in 13 long-term survivors (greater than 3 months). ECGs were obtained daily for the first 70 days 8- and 24-hour ambulatory electrocardiographic monitoring was performed 3 months after the transplantation and every 6 months thereafter. Junctional rhythm occurred during the early transplant period (less than 70 days) in nine of 13 patients. Complex premature ventricular depolarizations (Lown grade III or higher) were present in the late transplant period (greater than 70 days) in all five patients in whom severe coronary artery disease was found in the donor heart at postmortem, compared with two of the eight remaining patients (six survivors and two patients who died but did not have coronary artery disease at postmortem) (p less than 0.05). The high prevalence of junctional rhythm in the early transplant period appeared to be due to sympathetic denervation and reversible surgical damage to and ischemia of the sinus node region of the donor heart. Routine ambulatory electrocardiographic monitoring detected complex premature ventricular depolarizations, which were a sensitive marker for the subsequent mortality related to accelerated atherosclerosis of chronic rejection in the donor heart.

Adult↗
PubMed1981

Effects of intracoronary streptokinase in acute myocardial infarction.

Intracoronary streptokinase (SK) was administered to 11 patients with evolving acute transmural myocardial infarction 5.5 +/- 0.4 hours from the onset of symptoms. Ten patients (91%) had total coronary occlusion, and one had subocclusion of the vessel corresponding to the ECG site of infarction. Intracoronary nitroglycerin failed to restore patency of total occlusion in all patients. In 9 of 11 patients (82%), patency was restored or improved with intracoronary SK. Thrombolysis was successful in 8 of 11 patients (73%), and one patient with transient patency developed acute reocclusion. Average time from SK infusion to reperfusion was 24 +/- 7 minutes. Patients with successful thrombolysis had patency initially restored at a dosage of 61,000 +/- 15,000 IU of SK and received a total dosage of 136,000 +/- 17,000 IU. Patency persisted at late study in six of eight patients, and two patients developed late reocclusion. Successful thrombolysis was associated with significant improvement in left ventricular ejection fraction (LVEF) from early to late study, in contrast to deterioration of LVEF in patients with unsuccessful recanalization (p less than 0.001). Systemic fibrinolytic activity occurred in 8 of 11 patients at a mean dosage of 125,000 +/- 15,000 IU of SK and was unassociated with significant bleeding. Significant decrease in hemoglobin concentration in the early hospital phase occurred in patients receiving SK but did not differ from decreases occurring in a matched control population receiving conventional therapy for infarction. Thus intracoronary thrombolysis with SK was successful in the majority of patients during the early phase of evolving transmural infarction, and successful thrombolysis was associated with significant improvement in LVEF. Systemic fibrinolysis occurs in most patients despite small total doses of SK, and the significant decrease in hemoglobin in these patients may be unrelated to SK, since similar changes occurred in a control population receiving conventional therapy.

Cardiac Catheterization↗
PubMed1981

Characterisation of the excitation-contraction coupling system of the hypothermic myocardium following ischaemia and reperfusion.

The excitation-contraction coupling system of the globally ischaemic, hypothermic myocardium (60 min at 10 to 16 degrees C; I, n = 7) was studied by evaluating the functional integrity of the sarcoplasmic reticulum (SR) and the myofibrils (M). Comparison was made to the identical model followed by reperfusion (R, n = 7) and to sham-operated, time-matched controls (C, n = 7). Calcium uptake velocity from both the 60 min ischaemic group (I) and the reperfusion group (R) was significantly depressed (c = 0.960 +/- 0.05, I = 0.535 +/- 0.033, R = 0.662 +/- 0.035 micromolCa2+ . mg-1 . min-1, P less than 0.01). In contrast, SR . CA2+-ATPase activity was not affected by the hypothermic, ischaemic process (C = 1.150 +/- 0.08, I = 1.338 +/- 0.199 mumol Pi . mg-1 . min-1) but exhibited a small, significant depression after reperfusion (R = 0.940 +/- 0.04 mumol Pi . mg-1 . min-1, P less than 0.05). Myofibrillar pCa-ATPase curves in both experimental groups were significantly depressed (maximal ATPase activity: C = 0.18 +/- 0.01, I = 0.125 +/- 0.005, R = 0.115 +/- 0.01 mumol Pi . mg-1 . min-1; P less than 0.01). Kinetic analysis of the myofibrillar pCa-ATPase data, utilising double reciprocal plots, demonstrated an increase in injury in the hypothermic myocardium results from a breakdown of those subcellular structures responsible for the maintenance of the excitation-contraction coupling system. The ischaemic period, rather than reperfusion seems to be the major contributing factor in this sequence of pathological events.

Animals↗
PubMed1981

Excitation-contraction coupling in hypothermic ischemic myocardium.

The excitation-contraction coupling system of the global ischemic hypothermic myocardium was studied by evaluating the functional integrity of the isolated sarcoplasmic reticulum (SR) and myofibrils and determining glycogen decay 30 and 60 min after the onset of surgically induced global ischemia. Calcium uptake by the SR from both the 30- and 60-min groups was depressed (control 0.940 +/- 0.05, 30 min 0.430 +/- 0.033, 60 min 0.535 +/- 0.033 mumol Ca2+ . mg-1 . min-1; P less than 0.001). In contrast SR Ca2+-ATPase activity was not different in the three groups (control 1.150 +/- 0.080, 30 min 1.468 +/- 0.025, 60 min 1.338 +/- 0.199 mumol Pi . mg-1 . min-1; P greater than 0.2). Glycogen decay in the hypothermic group was depressed compared to control (control 7.52 +/- 2.01, 30 min 6.152 +/- 1.16, 60 min 5.814 +/- 1.76 mumol glycogen/mg myocardium; P less than 0.05). Myofibrillar pCa-ATPase curves in both hypothermic ischemic groups were depressed (maximal ATPase activity; control 0.160 +/- 0.028, 30 min 0.1130 +/- 0.01, 60 min 0.127 +/- 0.008 mumol Pi . mg-1 . min-1; P less than 0.01). Kinetic analysis of the myofibrillar pCa-ATPase data, utilizing double-reciprocal plots, demonstrated an increase in Km for the hypothermic ischemic groups. It is concluded that the excitation-contraction coupling system of the hypothermic ischemic myocardium at 1 h is characterized by a defect in the calcium transport system of the sarcoplasmic reticulum with preservation of the Ca2+-ATPase, a depression of the myofibrillar ATPase activity, a decrease in affinity, and the preservation of adequate glycogen stores. It is hypothesized that these defects may explain an observed depression in myocardial function following reperfusion.

Adenosine Triphosphatases↗