Myocardial Calcium Content Research Articles

Myocardial tissue pCO2 and calcium content during ventricular fibrillation and reperfusion periods.

Forty-one patients who underwent cardiac surgery under conditions of systemic hypothermia and intermittent cold crystalloid potassium cardioplegia were studied, in order to elucidate the effects of ventricular fibrillation and reperfusion on the myocardium, by using the intramyocardial pCO2 and temperature sensor. All patients were assigned to 2 groups, namely; group A (21 cases), in which the time between the aorta declamping and defibrillation was under 10 minutes, and group B (20 cases) in which the time was over 10 minutes. In both groups A and B, myocardial pCO2 increased at the rate of 3.58 +/- 1.70 and 2.16 +/- 0.62 mmHg/min (p less than 0.05) after aorta declamping, respectively and the myocardial pCO2 decreased at the rate of 5.59 +/- 0.60 and 4.18 +/- 0.76 mmHg/min (p less than 0.05) after defibrillation, respectively. In group A, the myocardial calcium content, pre-CPB (cardio pulmonary bypass) was 10.98 +/- 1.62 nmol/mg/dry weight and at the time of aorta declamping it was 15.90 +/- 1.81 nmol/mg/dry weight (p less than 0.05). In group B, the myocardial calcium content, pre-CPB, was 14.62 +/- 2.15 nmol/mg/dry weight and at the time of aorta declamping it was 18.23 +/- 4.36 nmol/mg/dry weight (p less than 0.05). At both three and six hours after the operation, the left ventricular work index per minute (LVWI) in group A showed better cardiac pump function than that in group B. We therefore conclude that when reperfusion is encountered, acidosis can be minimized by prompt defibrillation.

Diltiazem and verapamil reduce the loss of adenine nucleotidemetabolites from hypoxic hearts

The present study was undertaken to elucidate possible mechanisms for a protection of myocardial cells from hypoxia-induced derangements in cardiac function and metabolism by calcium antagonists. For this purpose, rabbit hearts were perfused for 20 min under hypoxic conditions in the presence of 312 ng/ml diltiazem or 125 ng/ml verapamil, and then for 45 min under reoxygenated conditions. Metabolic changes in the myocardium and the perfusate were examined throughout. Hypoxia induced a marked decline in myocardial high-energy phosphates and an immediate release of ATP metabolites, such as adenosine, inosine and hypoxanthine, from the perfused heart. These changes were effectively depressed by diltiazem and verapamil. Hypoxia and subsequent reoxygenation resulted in a release of creatine phosphokinase from the heart, which was completely inhibited by the treatment with either diltiazem or verapamil. Myocardial calcium contents were increased by 20 min-hypoxic perfusion. Both diltiazem and verapamil are capable of preventing hypoxia-induced increase in the transmembrane flux of cellular components, which may be beneficial for the preservation of substances necessary for the ATP regeneration after hypoxia and for the inhibition of calcium overload in cardiac cells.

Myocardial calcification and cardiac dysfunction in chronic renal failure1

Purpose Myocardial calcium content may have clinical importance in end-stage renal disease (ESRD), but it is difficult to detect during life. Our goal was to assess the effect of myocardial calcium content on left ventricular ejection fraction (LVEF) in uremic patients undergoing dialysis. Patients and methods Energy subtraction radiography of the chest was used to measure myocardial calcium content in 43 patients undergoing dialysis, in 32 control subjects, and in nine patients with advanced cardiomyopathy. LVEF and left ventricular end-diastolic dimension were measured by two-dimensional echocardiography. The concentration of parathyroid hormone was measured by radioimmunoassay; calcium-phosphorus product, alkaline phosphatase, and serum bicarbonate were also assessed. Results Patients undergoing dialysis had a greater myocardial calcium content than control subjects [262 ± 15.4 (mean ± SE) versus 187 ± 8 mg/cm2, p < 0.05]. Ten patients with the highest myocardial calcium content (Group I) had the lowest LVEF values and highest left ventricular end-diastolic dimension. Significant inverse linear associations between LVEF and myocardial calcium content (r = −0.425, p = 0.013) and between parathyroid hormone concentration and LVEF (r = −0.352, p = 0.047) were noted. There was no association between parathyroid hormone concentration and myocardial calcium content. Stepwise regression analysis showed a strong positive correlation between myocardial calcium content and calcium-phosphorus product, vascular calcification, race (black), and parathyroidectomy. Similar analysis shows that LVEF was significantly associated with myocardial calcium content, lung calcium, calcium-phosphorus product, and race (black). Conclusion We suggest that increased myocardial calcium content results from poor calcium and phosphorus control and may be enhanced by parathyroid hormone hyperactivity. Increased myocardial calcium content is strongly associated with myocardial dysfunction in patients undergoing dialysis. Myocardial calcium content may have clinical importance in end-stage renal disease (ESRD), but it is difficult to detect during life. Our goal was to assess the effect of myocardial calcium content on left ventricular ejection fraction (LVEF) in uremic patients undergoing dialysis. Energy subtraction radiography of the chest was used to measure myocardial calcium content in 43 patients undergoing dialysis, in 32 control subjects, and in nine patients with advanced cardiomyopathy. LVEF and left ventricular end-diastolic dimension were measured by two-dimensional echocardiography. The concentration of parathyroid hormone was measured by radioimmunoassay; calcium-phosphorus product, alkaline phosphatase, and serum bicarbonate were also assessed. Patients undergoing dialysis had a greater myocardial calcium content than control subjects [262 ± 15.4 (mean ± SE) versus 187 ± 8 mg/cm2, p < 0.05]. Ten patients with the highest myocardial calcium content (Group I) had the lowest LVEF values and highest left ventricular end-diastolic dimension. Significant inverse linear associations between LVEF and myocardial calcium content (r = −0.425, p = 0.013) and between parathyroid hormone concentration and LVEF (r = −0.352, p = 0.047) were noted. There was no association between parathyroid hormone concentration and myocardial calcium content. Stepwise regression analysis showed a strong positive correlation between myocardial calcium content and calcium-phosphorus product, vascular calcification, race (black), and parathyroidectomy. Similar analysis shows that LVEF was significantly associated with myocardial calcium content, lung calcium, calcium-phosphorus product, and race (black). We suggest that increased myocardial calcium content results from poor calcium and phosphorus control and may be enhanced by parathyroid hormone hyperactivity. Increased myocardial calcium content is strongly associated with myocardial dysfunction in patients undergoing dialysis.

Effects of amiodarone and thyroid dysfunction on myocardial calcium, serum calcium and thyroid hormones in the rat.

1 Myocardial calcium content was found to be elevated and serum calcium reduced in hypothyroid rats. 2 Treatment of rats with amiodarone at either 30 mg kg-1 or 150 mg kg-1 daily did not result in any significant changes in myocardial or serum calcium. 3 The administration of amiodarone to hypothyroid rats attenuated the changes in serum but not myocardial calcium, suggesting that amiodarone may exert a thyroid hormone-like effect in the hypothyroid state. 4 The administration of amiodarone to thyroid hormone-treated rats resulted in attenuation of the effects on serum calcium and calculated intracellular calcium; this was consistent with an antagonistic interaction between amiodarone and thyroid hormones. 5 Administration of amiodarone resulted in significant changes in circulating thyroid hormone levels in the rat; triiodothyronine was reduced and basal thyrotrophin elevated compared to euthyroid controls. Serum thyroxine was not changed; this is in contrast to the effects in man. 6 Amiodarone does not exert its anti-arrhythmic action via changes in total myocardial calcium content in the euthyroid rat; nonetheless the described interactions between the drug and thyroid hormones may be involved in its mechanism of action.

Verapamil protects against progression of experimental chronic renal failure

Chronic administration of verapamil (Ver) decreases nephrocalcinosis and tubular ultrastructural abnormalities in the remnant model of chronic renal disease. In the present study, the effect of chronic Ver administration on renal function, renal histology and mortality after subtotal nephrectomy was examined. Fourteen days after staged subtotal nephrectomy rats were paired according to renal functional impairment, mean arterial pressure (MAP), and body weight. Rats were pair fed and received either Ver (0.1 micrograms/g sc bid, N = 10) or saline (0.1 ml sc bid, N = 10) for up to 23 weeks. Both members of each pair were sacrificed shortly before the uremic death of controls. At sacrifice, rats treated with Ver had a lower serum creatinine (2.29 vs. 2.99 mg/dl, P less than 0.05) and a higher creatinine clearance (318 vs. 164 microliters/min, P less than 0.05) than controls. In a second experiment, survival was superior in rats treated with Ver than in controls from week seven (P less than 0.0025 by week 14). Serum creatinine was higher at week 10 in control rats (1.68 vs. 1.10 mg/dl, P less than 0.05). MAP was no different between the two groups, irrespective of the time between Ver administration and the measurement of MAP. Histological damage and nephrocalcinosis were worse, and renal and myocardial calcium content was higher in controls. In conclusion, independent of any effect on systematic MAP, chronic administration of Ver protects against renal dysfunction, histological damage, nephrocalcinosis and myocardial calcification, and improves survival in the remnant model of chronic renal disease.

Parathyroidectomy, cardiovascular reactivity and calcium distribution in aorta and heart of spontaneously hypertensive rats.

In order to elucidate the mechanisms by which parathyroidectomy (PTX), performed in young spontaneously hypertensive rats (SHR), delays the development and attenuates the level of hypertension, we studied, in vivo, cardiovascular reactivity (CVR, blood pressure response to bolus noradrenaline administration), aortic calcium distribution and cardiac calcium content in SHR with or without parathyroid glands. PTX was performed in 6-week-old animals and experiments were done in pretreated anaesthetized animals 2 and 22 weeks after surgery. A significantly decreased CVR was observed 22 weeks after PTX in SHR-PTX as compared with controls. These data are not specific for hypertensive animals since similar data are also obtained on normotensive Wistar rats treated in an identical fashion. In addition, after PTX in SHR and Wistar rats myocardial (auricle and ventricle) calcium content was more rapidly reduced (after 2 weeks) than aortic membrane-bound and cellular calcium fractions. The present studies established that PTX decreased CVR and alters calcium content and distribution in the cardiovascular systems of rats from hypertensive and normotensive strains. Furthermore, the results confirm a requirement for the parathyroid glands in the pathogenesis of spontaneous hypertension in SHR and for the normal CVR.

Calcium uptake during insulin-aggravated ischemic myocardial contracture in the rat heart.

Perfusion of isolated, nondiabetic rat hearts with high concentrations of regular insulin (10 mU/ml) produced earlier onset of myocardial contracture during ischemia than control perfusions without insulin. High insulin concentrations also increased total myocardial calcium content (p less than .001) and myocardial Ca-45 uptake postischemia (p less than .05). Insulin perfusion before ischemia did not enhance calcium uptake. These results support the hypothesis that insulin may increase calcium movement across myocardial cell membranes, which may lead to increased ischemic contracture. Insulin-aggravated myocardial ischemia in cardiothoracic surgery and cardiac resuscitation deserves further investigation.

Effects of propranolol on myocardial damage resulting from coronary artery occlusion followed by reperfusion

To evaluate the effects of propranolol on myocardial metabolism after coronary reperfusion, serial measurements of myocardial creatine kinase (CK) and calcium (Ca) contents and CK and tactic acid (LA) concentrations in coronary sinus blood were carried out in 33 open-chest dogs. The left anterior descending coronary artery was occluded for 60 minutes and was then reopened. Twelve of the dogs were given propranolol before occlusion. Reperfusion for 30 minutes in dogs with and without propranolol pretreatment resulted in reduced myocardial CK in the ischemic region and rapidly elevated plasma CK and LA. However, when compared with the control group, the propranolol-treated group showed smaller changes in myocardial CK and plasma LA. Myocardial Ca in the ischemic region was significantly higher than that in the nonischemic region in the control group, but not in the propranolol-treated group. It was concluded that propranolol was protective against myocardial damage resulting from coronary occlusion followed by reperfusion.

開心術におけるReperfusion Injuryの予防に関する実験的研究

Myocardial reperfusion after ischemia and anoxia produces some changes in myocardial metabolism and ultrastructure which may lead to myocardial dysfunction known as reperfusion injury. However the pathogenesis of reperfusion injury is multifactorial and clear m echanisms responsible for its manifestation have not been presented. The present study was designed to investigate if reperfusion injury could be avoid or reduced by an appropriate pretreatment just before reperfusion.Isolated hearts from fourty seven mongrel dogs were exposed to 30 minutes normothermic global ischemia in the Ringer-lactate solution maintained at 37°C. According to the types of a pretreatment just before reperfusion, the experiment was classified into four groups (Group I of no pretreatment as control group, Group II of pretreatment with 500ml of hyperkalemic (K 25mEq/l), alkalotic (pH7.8) Ringer lactate solution, Group III of pretreatment with hyperkalemic (K 25mEq/l), alkalotic (pH7.8) diluted autologus blood (Ht 20%), and Group IV of pretreatment with calcium-anntagonist (Verapamil) contained in hyperklemic (K 25mEq/l)alkalotic (pH 7.8) Ringer lactate solution. Moreover, Group IV was divided into four subgroups depending on the volume of Verapamil (IV of 0.04mg/l of Verapamil, IV b of 0.02mgit, IV c of 0.015mg/l, IV d of 0.01mg/t). After the pretreatment of 5 minutes infusion to the coronary arteries in each group except Group I,30 minutes reperfusion and one hour working were performed with the cardiac perfusion apparatus for isolated heart.In Group I reperfused with diluted oxygenated blood of 20 to 25% of Ht and of pH7.4 at 37 °C, oxygen extraction was higher, but excess lactate was positive and redox potential (ΔEh) was negative at the early period of reperfusion. Positive excess lactate with negative ΔEh continued in the reperfusion period, although oxygen extraction was significantly low. These results suggest that augumented oxygen uptake in the initial reperfusion results in reperfusion injury. The value of CPK-MB in coronary venous blood was significantly higher and myocardial ATP was lower with increased myocardial calcium content and poor mitochondrial calcium uptake all through the period of reperfusion and working. Left ventricular function could not achieve to measure at the period. of 30 to 60 minutes after the beginning of working in some case of group I and it showed the poorest recovery if it could be measured. These results also suggest that these prolonged impairments arise from reperfusion injury. Electronmicroscopically, destruction of mitochondria with margination of nuclear chromatin and sometimes with a deposit of calcium in mitochondria was demonstrated. These morphological changes were irreversible even the period of working. In contrast, group II showed persistently higher oxygen extraction with negative excess lactate and positive ΔEh except the initial period of reperfusion, improved preservation of myocardial ATP, rapid decrease in myocardial calcium content with good mitochondria' calcium uptake, and best recovery of left ventricular function indicating best protective effect for reperfusion injury. Particularly, the value of myocardial calcium content returned to normal at the working period, although those in other 3 groups were significantly higher. Apparently, group II showed significantly better mitochondrial calcium uptake and exhibited greatest left ventricular stroke work index at lower left atrial pressure at the working period. Electron-microscopically, structural integrity was well preserved and essentially normal at the end of working period in this group.

Effects of hypothyroidism and chronic amiodarone therapy on myocardial calcium content

Effects of hypothyroidism and chronic amiodarone therapy on myocardial calcium content

Effect of chronic renal failure on heart. Role of secondary hyperparathyroidism.

This study examined the effects of chronic renal failure in rats with and without parathyroid glands on myocardial energy production, transfer and utilization as well as on cardiac index. Chronic renal failure was produced by 7/8 nephrectomy in rats weighing between 240 and 350 g with intact parathyroid glands (CRF-control) and in parathyroidectomized (CRF-PTX) rats maintained normocalcemic. The data were compared to results obtained in intact rats and in normocalcemic parathyroidectomized rats with normal renal function. There were significant (p less than 0.01) decrements in myocardial content of ATP and creatine phosphate, mitochondrial oxygen consumption, and in the activity of both mitochondrial and myofibrillar creatine phosphokinase in CRF-control rats as compared to normal animals. The myocardial calcium content and the 45Ca uptake in CRF-control rats were significantly (p less than 0.01) higher than in normal rats. In CRF-PTX animals, the myocardial content of ATP, mitochondrial oxygen consumption, 45Ca uptake and calcium content were normal, but PTX did not normalize the activity of mitochondrial and myofibrillar creatine phosphokinase. Parathyroidectomy in rats with normal renal function was associated with a significant reduction in the activity of creatine phosphokinase of myocardial mitochondria and myofibrils. There was a significant (p less than 0.01) decrease in cardiac index in CRF-control rats as compared to normal animals, and cardiac index did not return to normal in CRF-PTX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of ICRF 159 on adriamycin-induced cardiomyopathy in rats

The effect of ICRF 159 on adriamycin (ADR) cardiotoxicity and on total myocardial calcium content was examined in rats. ICRF 159 did not increase the survival time of ADR-treated animals; however the histological findings showed a significant prevention of ADR-induced cardiomyopathy (CMP) by ICRF. The total myocardial calcium content of animals treated with ADR was significantly higher, while no significant difference was seen in animals pretreated with ICRF 159 as compared with controls. As these findings suggested a role of calcium in ADR CMP and in the pharmacological action of ICRF in this disease, we also tested a closely related chelating agent, EDTA. This molecule decreased myocardial calcium levels in ADR-treated animals almost to normal values; however the histological cardiac alterations were not prevented.

Verapamil prevents isoproterenol-induced cardiac failure in the rat

Virgin, male Sprague-Dawley rats were used to study the production of cardiac failure by a single subcutaneous injection of 85 mg/kg dl-isoproterenol (ISO) and the possible preservation of cardiac function by a pre-treatment of 50 mg/kg verapamil (VER) 5 min prior to 85 mg/kg ISO. At 24 hrs after drug injections cardiac function was assessed in anesthetized, open-chest rats by the measurement of cardiac output and by a volume loading of the heart with a 2 min, 15.3 ml/min jugular vein infusion of Tyrode's solution. Peak cardiac index and peak stroke index were depressed by ISO. VER completely prevented these signs of ISO-induced cardiac failure. A second group of rats was sacrificed 24 hrs after ISO and VER-ISO and their left ventricular calcium contents were determined. ISO caused a significant increase in left ventricular calcium content. VER attenuated the ISO-induced increase in myocardial calcium content, but did not prevent it. This data raises questions as to whether VER's property as a transarcolemmal calcium flux inhibitor was the mechanism of preservation of cardiac function following ISO administration. It is possible that VER may have preserved cardiac function by altering ISO-induced hemodynamic changes in the rat.

Pathophysiological significance of coronary collaterals for preservation of the myocardium during coronary occlusion and reperfusion in anaesthetised dogs.

The significance of pre-existing coronary collaterals for preservation of the myocardium during coronary occlusion and reperfusion was studied in anaesthetised open-chest dogs. The extent of myocardial ischaemic damage was assessed by the accumulation of calcium in the central zone of the ischaemic area and the size of myocardial infarct by the p-nitroblue tetrazolium staining method. Myocardial creatine kinase release was considered as an index reflecting both the extent of ischaemic myocardial damage and the size of the infarct. Reperfusion with the arterial blood of a main branch of the left coronary artery following the 60 min occlusion aggravated the ischaemic myocardial damage, as evidenced by exaggerated cardiac irregularity, myocardial calcium accumulation, and creatine kinase release. The myocardial calcium content and the logarithm of the creatine kinase release during reperfusion were linearly related to the infarct size. These parameters of myocardial damage were inversely related to the retrograde blood flow through the peripheral end of the occluded artery or the ratio of the retrograde-to-orthograde flow, indicating that the pre-existing collaterals influence preservation of the ischaemic myocardium. Thus, it is suggested that the collateral flow available during an ischaemic episode determines the viability of the myocardial cells during ischaemia, and in turn during reperfusion.

Reduced myocardial actomyosin adenosine triphosphatase activity in the ageing male Fischer rat.

Actomyosin was extracted from myocardial homogenates from male rats of different ages of a long-inbred Fischer rat colony maintained under controlled conditions of temperature, humidity, and light. ATPase specific activity rose to a maximum at 2 months of age; this was followed by a progressive decline by about 25% at 16 months of age. However, the extractable actomyosin remained constant during this period. This loss in actomyosin ATPase specific activity is in good agreement with previously reported decrements in both stroke index and myocardial calcium content and an increase in myocardial contraction duration in aged rats.

Further investigations on the mechanism of the inotropic action of prostaglandin E 1 in relation to the ion balance in frog heart

Summary It has been shown that Prostaglandin E1 (PGE1) can antagonize the effect of potassium ions on the frog heart only when an adequate amount of calcium ions are present in the perfusing fluid, and that no direct antagonistic action on potassium can be demonstrated. In order to clarify which mechanism is primarily involved in the cardiac action of PGE1, the relationship between PGE1 and intracellular exchangeable calcium has been investigated. PGE1 brings about a significant increase in the rate of uptake of Ca-45, whereas the total myocardial calcium content and the net amount of cellular exchangeable calcium is not affected. These results could be explained by an increase of the membrane permeability to Ca++.