Yoshihisa Ito

Intracellular calcium and myocardial contractility V. Calcium uptake of sarcoplasmic reticulum fractions in hypertrophied and failing rabbit hearts

To evaluate calcium uptake in the sarcoplasmic reticulum (SRF) in the hypertrophied and failing myocardium, SRF was prepared from hearts of rabbits with experimentally produced aortic insufficiency (AI). In SRF preparations from the hypertrophied hearts of animals killed shortly (2 weeks) after AI production calcium uptake was normal, 0.146 ± 0.001 compared to control values of 0.137 ± 0.010 μmol×mg−1×min−1. However, calcium uptake was reduced in SRF preparations from hypertrophied hearts removed from animals later (4 to 7 weeks) after AI production. In this latter group, some of the animals had no pathologic evidence of left ventricular failure but a significant reduction of calcium uptake was observed, 0.086 ± 0.002 μmol×mg−1×min−1 (P < 0.01). In other animals, with clear pathologic findings of failure, further reduction of calcium uptake was observed, 0.058 ± 0.006 μmol×mg−1×min−1. Ouabain was not effective in reversing these depressed activities, either when given in vivo or in vitro. These findings indicate that the decrease in SRF function is not a necessary accompaniment of ventricular hypertrophy, but may develop later as hypertrophy becomes more extensive and/or heart failure occurs. It remains to be demonstrated whether or not the abnormality of SRF uptake of calcium initiates the onset of heart failure or is in fact the result of the development of such depressed cardiac function.

Intracellular calcium and myocardial contractility. IV. Distribution of calcium in the failing heart.

Abstract Myocardial calcium and its distribution in intracellular fractions were measured in chronic heart failure occurring in rabbits with experimental aortic insufficiency. In these animals heart failure was characterized by the presence of pulmonary congestion and edema and the development of diminished myocardial contractility. Hearts were analyzed for calcium contents either after perfusion in vitro or immediately after removal from the animals. Total myocardial calcium was similar in control and failing hearts after in vitro perfusion and was only minimally increased in those failing hearts which were not perfused. However, calcium was elevated in intracellular fractions prepared from failing hearts. An increase of calcium was found in mitochondria of hearts perfused in vitro from a control of 10.9 ± 0.5 to 16.3 ± 1.6 nmol/mg. Similar increments in mitochondrial calcium were seen in the failing hearts which were not perfused but analyzed immediately after removal from the animal. Changes of calcium in the microsomal fractions were more difficult to interpret because of the greater heterogeneity of these fractions. These findings indicate that, although the total amount of calcium available to the myocardial cell is not diminished in the failing heart, a change of intracellular calcium metabolism is present, leading to an altered distribution of this cation with greater amounts accumulated in mitochondria. These changes may be causally related to the reduced contractility of the failing heart by limiting the amount of calcium available to initiate contraction.

Compression of right ventricular out-flow due to localized hematoma after coronary perforation during PCI

Although coronary perforation can cause tamponade during percutaneous coronary intervention (PCI), this is unusual for patients previously undergoing coronary artery bypass graft surgery (CABG) due to pericardial adhesions. We report here on a rare case of right ventricular out‐flow obstruction complicating PCI in a patient with a previous CABG. Cathet Cardiovasc Intervent 2003;58:202–206.

Calcium Supplementation in Salt-Dependent Hypertension

To clarify the mechanism of the antihypertensive effect of oral Ca loading, we studied the effect of Ca supplementation on salt-induced blood pressure elevations in patients with essential hypertension and DOCA-salt hypertensive rats. When the diet was changed from low to high salt (300 mEq/day), the percent increase in mean blood pressure was smaller (p less than 0.01) in the Ca-supplemented (2,160 mg/day) patients than in the Ca-restricted (250 mg/day) ones. Oral Ca loading resulted in a smaller weight gain, a greater urinary sodium excretion, and an increase in red cell Mg. In the experimental study, high Ca (4% CaCl2) intake attenuated the blood pressure elevation in DOCA-salt-treated rats, accompanied with an increase in urinary sodium excretion, with the resultant attenuation in intra- and extracellular sodium retention. The decrease in catecholamine contents of hearts was improved, and a higher survival rate was observed in Ca-supplemented DOCA-salt rats. The results suggest that Ca supplementation may prevent a rise in BP in salt-dependent hypertension by inducing natriuresis with the resultant attenuation in sodium retention. The altered intracellular Mg level in hypertensive patients and the normalization of enhanced sympathetic nervous activity in DOCA-salt rats may, in part, be involved in its mechanism.

Protective effect of coenzyme Q10 on thyrotoxic heart in rabbits

SummaryAn excess of thyroid hormone is known to produce cardiac dysfunction and failure, i.e., thyrotoxic heart. We studied the protective effect of coenzyme Q10 (CoQ10) on the thyrotoxic heart in 29 rabbits. A group treated with 1-thyroxine sodium salt (T4; 167 µg/kg) for 3 weeks showed marked decreases in the myocardial content of norepinephrine (NE) and ATP (0.5±0.2 µg/g wet weight,P<0.05 and 31.1±2.6 nmol/mg protein,P<0.05, respectively) as compared with a group treated with CoQ10 solvent (2 ml/kg) for 3 weeks (1.1±0.1 µg/g wet weight and 45.7±4.7 nmol/mg protein). The mitochondrial Ca2+ content of the T4 group showed significant increases (21.3 ± 0.6 nmol/mg protein,P<0.05) compared with the solvent group (18.2±0.8 nmol/mg protein), while the total tissue Ca2+ content of the T4 group was unchanged compared with the solvent group. These biochemical derangements suggest that T4-treated rabbits were in a state of cardiac dysfunction. In contrast, a group which was assigned to concomitant treatment of T4 and CoQ10 (5 mg/kg) for 3 weeks showed no reductions in NE and ATP (0.9±0.2 µg/g wet weight and 44.6±1.9 nmol/mg protein, respectively) and protected an increase in the mitochondrial Ca2+ content (18.2±1.2 nmol/mg protein). A group treated with CoQ10 (5 mg/kg) for 3 weeks showed no changes in myocardial NE, ATP, and Ca2+ content in the mitochondria. These results suggest that exogenously administered CoQ10 may protect against biochemical derangements in the thyrotoxic heart.