Hideyuki Ohta

Calcium Overload-Induced Myocardial Damage Caused by Isoproterenol and by Adriamycin: Possible Role of Taurine in its Prevention

Calcium ion (Ca2+) is essential for excitation-contraction coupling and for maintenance of cell integrity in the myocardium. On the other hand, it is clear that cytosolic Ca2+ loading may be the first event leading to cell death in certain forms of myocytic injury, such as Ca2+ paradox and isoproterenol (ISO) toxicity. The Ca2+ overload injury is characterized by an exhaustion of tissue high-energy phosphate, massive release of enzymes and extensive ultrastructural damage, as well as excessive influx of Ca2+ into the myocardial cells.

Protective effect of taurine against isoprenaline-induced myocardial damage

SummaryThe effect of the sulfur amino acid, taurine, was examined on histological and biochemical changes induced by a toxic dose of isoprenaline in chick hearts. Isoprenaline treatment (80 or 240 mg/kg id twice daily for 4 days) caused a dose-dependent increase in heart weight and decrease in myocardial ATP. Isoprenaline administration (240 mg/kg id twice daily) produced necrotic changes in hearts, such as eosinophilic degeneration, myolysis, interstitial oedema, fibrosis, and inflammatory cell infiltration. Substantial accumulation of calcium was also observed. Taurine content of the heart was not significantly decreased. Parenteral administration of taurine (200 mg/day for 7 days) partially protected against these necrotic changes induced by isoprenaline. It is suggested that the protective effect of taurine against isoprenaline-induced myocardial injury might be due in part to the prevention of the massive overloading with calcium which is thought to cause myocardial cell necrosis.

Beneficial effect of coenzyme Q on myocardial slow action potentials in hearts subjected to decreased perfusion pressure—hypoxia—substrate-free perfusion

SummaryCoenzyme Q, an important component of the electron transfer system in mitochondria, plays a central role in energy production aerobically. The effect of pretreatment with coenzyme Q10 (Co Q) on myocardial slow action potentials (APs) and accompanying contractions and on myocardial high energy phosphate content was studied in perfused hearts subjected to decreased perfusion pressure—hypoxia—substrate-free. Post-hatched chicks were treated i.p. with 10 mg/kg of Co Q daily for 5 days. To study the slow APs exclusively, the fast Na+ channels were voltage-inactivated by elevated K+ (25 mM) Tyrode solution. The Ca++-dependent slow APs were induced by elevating [Ca]0 to 5.4 mM; hearts were paced at a rate of 40 per min. Hearts which had been pretreated with Co Q were protected against the deleterious effect of decreased perfusion pressure—hypoxia—substrate-free perfusion on mechanical performance accompanying the slow Ca++−Na+ APs. The slow APs in hearts pretreated with Co Q were also less affected than were non-treated hearts. However, the myocardial ATP and total adenine nucleotides were not affected by exogenous Co Q. It was suggested that exogenous Co Q could protect against the decline of cardiac contractions via improved availability of slow APs during decreased perfusion pressure—hypoxia—substrate-free, independently of the cellular high energy phosphate level.

Enhanced suppression of myocardial slow action potentials during hypoxia by free fatty acids

Effects of free fatty acids (palmitate and linoleate) on myocardial contractility and slow action potentials (APs) were examined in Langendorff-perfused chick hearts. To study the slow APs exclusively, the fast Na+ channels were voltage-inactivated in elevated K+ (25 mM), and the concentration of Ca2+ ion was increased to 5.4 mM in order to induce slow APs. Palmitate (0.18, 0.54 or 0.72 mM) along with albumin (0.12 mM) was added to the perfusate. Albumin by itself did not affect contractility or the slow APs during normoxia and hypoxia. Under well oxygenated conditions, palmitate had no effect on contractility or the slow APs. However, palmitate accelerated the decline of contractility during hypoxia in a dose-dependent fashion. Hypoxia suppressed the slow APs, and palmitate and linoleate further exacerbated the suppression of slow APs produced by hypoxia. Nevertheless, palmitate and linoleate did not enhance the hypoxic reduction of the tissue high energy phosphate level. The present results suggest that free fatty acids elicit cardio-depressant effects on hearts through their direct action on the myocardial cell membrane (slow channels) rather than through any metabolic effects.