Myocardial Creatine Phosphokinase Research Articles

Clinical Characteristics and Prognosis of Life-Threatening Acute Myocardial Infarction in Patients Transferred to an Emergency Medical Care Center.

Patients with acute myocardial infarction (AMI) triaged as life-threatening are transferred to our emergency medical care center (EMCC). However, data on these patients remain limited. We aimed to compare the characteristics and AMI prognosis of patients transferred to our EMCC with those transferred to our cardiovascular intensive care unit (CICU) using whole and propensity-matched cohorts.We analyzed the data of 256 consecutive AMI patients transferred from the scene to our hospital by ambulance between 2014 and 2017. The EMCC and CICU groups comprised 77 and 179 patients, respectively. There were no significant between-group age or sex differences. Patients in the EMCC group had more disease severity score and had the left main trunk identified as the culprit more frequently (12% versus 0.6%, P < 0.001) than those in the CICU group; however, the number of patients with multiple culprit vessels did not differ. The EMCC group had a longer door-to-reperfusion time (75 [60, 109] minutes versus 60 [40, 86] minutes, P< 0.001) and a higher in-hospital mortality (19% versus 4.5%, P < 0.001), especially from non-cardiac causes (10% versus 0.6%, P < 0.001), than the CICU group. However, peak myocardial creatine phosphokinase did not significantly differ between the groups. The EMCC group had a significantly higher 1-year post-discharge mortality than the CICU group (log-rank, P = 0.032); this trend was maintained after propensity score matching, although the difference was not statistically significant (log-rank, P = 0.094).AMI patients transferred to the EMCC exhibited more severe disease and worse overall in-hospital and non-cardiac mortality than those transferred to the CICU.

Perivascular fat attenuation index measured by coronary computed tomography angiography as a tool for assessment of ischaemia-causing lesions: a case report

BackgroundIt can be difficult to diagnose coronary artery disease in patients with acute coronary syndrome if coronary angiography does not identify stenosis. Coronary inflammation, which can contribute to the pathogenesis of coronary artery disease and acute coronary syndrome, can be quantified using the perivascular fat attenuation index. Furthermore, the perivascular fat attenuation index is a marker for all-cause mortality, cardiac-related mortality and impaired global coronary flow reserve.Case presentationHere we report a case of a patient presenting with symptoms of acute coronary syndrome. The patient had hypokinesis of the lateral-posterior wall of the left ventricle, decreased myocardial perfusion in the posterior wall myocardium and elevated myocardial troponin-T and creatine phosphokinase levels. However, coronary computed tomography angiography did not identify arterial stenosis. The patient did have an increased perivascular fat attenuation index, indicating coronary inflammation. Moreover, the fat attenuation index was higher around the left circumflex artery than around the right coronary artery or left anterior descending artery. Intravascular ultrasonography identified an intramural haematoma, leading to a diagnosis of type 3 spontaneous coronary artery dissection in the left circumflex artery.ConclusionsPerivascular fat attenuation index may be a useful tool to help identify and localise disease-causing lesions, and to direct further testing to confirm a diagnosis of spontaneous coronary artery dissection in acute coronary syndrome patients without significant arterial stenosis.

Inhibition of TNF-α and JNK Signaling Pathway Can Reduce Paclitaxel-Induced Apoptosis of Mouse Cardiomyocytes.

Paclitaxel (PTX) is a widely used chemotherapeutic drug for treating tumors. However, studies have shown that it can cause cardiac problems such as arrhythmia, myocarditis, chronic cardiomyopathy, and heart failure. Therefore, it is essential to study the mechanism behind the cardiotoxicity of PTX in tumor treatment. In this study, we initially injected PTX into mice to establish a myocardial cell apoptosis model to observe the degree of damage to mouse myocardium caused by PTX. Upon determining the levels of mouse myocardial creatine phosphokinase (CK), myokinase isoenzyme (CK-MB), aspartate transaminase (AST), and lactate dehydrogenase (LDH), we found that all of these levels showed apparent increases in mice treated with PTX. Further analyses of the TNF-α level and the expression of Jun N-terminal kinase (JNK) and Bcl-2 family-related proteins in myocardial tissue were performed. It was found that PTX increased the protein levels of TNF-α, Bax, p-JNK, and JNK in myocardial tissue but decreased the protein level of Bcl-2. After 1 month of PTX treatment in mice, we inhibited the expression of TNF-α and JNK proteins, which reduced the effect of paclitaxel on the apoptosis of mouse cardiomyocytes. The protein levels of Bax, p-JNK, and TNF-α in cardiomyocytes were reduced, while there was a relative increase in the Bcl-2 protein level. The findings suggested that inhibition of the NK signaling pathway and TNF-α can lessen the effect of PTX on mouse cardiomyocytes.

Kolaviron attenuates cardiovascular injury in fructose-streptozotocin induced type-2 diabetic male rats by reducing oxidative stress, inflammation, and improving cardiovascular risk markers

The prevalence of cardiovascular disease among type-2 diabetic patients has become a source of major concern world over. This study explored the protective effect of kolaviron, a bioflavonoid, against oxidative cardiovascular injury in fructose- streptozotocin-induced type 2 diabetic male Sprague Dawley rats. After acclimatization, induction, and confirmation of type-2 diabetes, kolaviron was administered for 28days, after which the animals were anesthetized with Isofor and euthanized. Blood from each rat were collected, and blood samples were then centrifuged for serum and plasma. Cardiac troponin I (cTnI), creatine kinase myocardial band (CK-MB), Creatine phosphokinase (CK), and insulin levels were immediately determined in serum, while remaining samples (serum, plasma, and organs) were stored in the bio-freezer at − 80 °C and 10% formalin for enzyme-link immunosorbent assay (ELISA), biochemical, molecular, and histopathological studies. The results show that type-2 diabetes induction with fructose and streptozotocin led to increased blood glucose levels, decreased insulin levels and cardiac antioxidant enzyme activities, increased malondialdehyde levels, cardiac biomarkers and pro-inflammatory cytokines levels, resulted in abnormal lipid profile, increased blood pressure and angiotensin-converting enzyme (ACE) activity, and decreased plasma endothelial nitric oxide synthase (eNOS) concentration. The histopathological examination of the cardiac tissue revealed severe lesion, hypertrophy, and myofibrils degeneration. However, administration of kolaviron for 28days remarkably improved these conditions. Hence the result from the study validates the potency of kolaviron, and suggests it could serve as an alternative to existing remedy in ameliorating or protecting against cardiovascular injury in type-2 diabetes.

Effect of short-term creatine monohydrate supplementation on indirect markers of cellular damage in young soccer players

Summary Purpose In recent years, creatine (Cr) supplementation has received great attention in both popular and scientific media. Nevertheless, there is anecdotal information on the side effects of this supplement. Hence, we hypothesized that Cr monohydrate (CrM) loading would induce increase in serum enzymes activity as indirect markers of cellular damage. Therefore, the present study was conducted to identify the effect of short-term Cr supplementation on serum lactate dehydrogenase (LDH), creatine phosphokinase (CK), and myocardial CK isoform (CK MB ) in young male soccer players. Methods Eighteen volunteer young male soccer players in a randomized and double-blind design were divided into two equal groups (Cr & Placebo groups). Creatine (CrM) group was ingested Cr supplementation (0.3 g/kg/d for 7 days), but placebo group (Pl) was not took any supplements. All subjects were participated in circuit weight training (eight exercises, three sets, 15 repetitions, and 60% one repetition maximum [1RM]). To identify enzymes activity (IU/L), venous blood samples were obtained before Cr loading and 24 h after last session of weight training, Moreover, VO 2 max each of subjects were obtained with 20 m Shuttle Run test. Data were expressed as mean (±SD) and analyzed by paired and independent t -tests using SPSS15 at P ≤ 0.05. Results The modest elevation of LDH activity in both groups were not significant following the short-term Cr supplementation, whereas, mean and changes range of CK ( P = 0.0004, t CK = 5.13) and CK MB ( P CKMB = 2.10) activities in CrM group were significantly higher than in Pl group ( P Conclusion The present results suggest that serum CK and CK MB activity as indirect markers of cellular damage increases by the oral short-term CrM supplementation in young male soccer players. Therefore, it can be concluded that CrM loading probably have significant adverse effects on serum indirect markers of cellular damage. Nevertheless, more research will be needed to determine effect of the short and long-term Cr supplementation on the other indirect markers of cellular damages in the future.

English

The cardioprotective effects of&nbsp;Tribulus teresstris&nbsp;(Tt), a medicinal herb, used in Indian system of medicine was evaluated in the Langendorff model of myocardial ischemia and reperfusion (I-R) injury. Tt (1, 2.5, 5, 10 mg/kg) was orally fed to healthy experimental rats once a day for 21 days followed by global ischemia and reperfusion injury. Biochemical parameters: lipid peroxidation product thiobarbituric acid reactive substances (TBARS), endogenous antioxidant: glutathione, antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GSHPx)) and myocardial enzyme creatine phosphokinase (CPK) were evaluated. To correlate the biochemical derangement and altered cardiac performance during I-R, changes in the hemodynamic variables heart rate (HR) and coronary perfusion pressure (CPP) was measured. Myocardial apoptotic was quantified using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. The expression of anti-apoptotic protein Bcl-2, pro-apoptotic protein Bax, enzyme: Caspase 3 and heat shock protein (HSP) in cardiac myocytes was detected by immunohistochemistry. As compared with sham group, the CPP, TBARS levels, myocardial apoptosis, expression of Caspase 3, Bax, heat shock protein (HSP 72) proteins were increased significantly in I-R control group. Tt pre-treatment significantly restored the antioxidant network of the myocardium, reduced myocardial apoptosis, Bax, HSP 72 protein expression. These beneficial effects also translated into favourable hemodynamic effects. Histopathological studies and myocardial CPK content further confirmed the cardioprotective effects of Tt (2.5 mg/kg) in the experimental model of I-R injury. &nbsp; Key words:&nbsp;Apoptosis, ischemia and reperfusion, medicinal herbs,&nbsp;Tribulus teresstris, antioxidants.

Bacopa monniera protects rat heart against ischaemia–reperfusion injury: role of key apoptotic regulatory proteins and enzymes

Rat isolated hearts were perfused in a Langendorff model to study the cardioprotective effects of Bacopa monniera, a medicinal herb used in the Indian system of medicine, on cardiomyocyte apoptosis and antioxidant status following ischaemia-reperfusion (I-R) injury. Forty-eight rats were randomly divided into four groups (12 in each group): sham group (no ischaemia-reperfusion injury), B. monniera control group (orally fed B. monniera at a dose of 75 mg/kg, for three weeks); ischaemia-reperfusion control group(subjected to ischaemia-reperfusion-induced myocardial injury) and B. monniera-treated group (same protocol as ischaemia-reperfusion control group except that rats also fed B. monniera). Post-ischaemic reperfusion injury resulted in significant cardiac necrosis, apoptosis, depression of heart rate, decline in antioxidant status and elevation in lipid peroxidation. Oral administration of B. monniera per se for three weeks to healthy rats caused augmentation of myocardial antioxidants, superoxide dismutase, catalase and glutathione, along with induction of heat shock protein 72 (HSP72). Ischaemia-reperfusion-induced biochemical and histopathological perturbations were significantly prevented by B. monniera (75 mg/kg) pre-treatment. Interestingly, B. monniera also restored the antioxidant network of the myocardium and reduced myocardial apoptosis, caspase 3 and Bax protein expression. Histopathological studies and myocardial creatine phosphokinase content further confirmed the cardioprotective effects of B. monniera (75 mg/kg) in the experimental model of ischaemia-reperfusion injury. The study provides scientific basis for the putative therapeutic effect of B. monniera in ischaemic heart disease.

Relationship Between Systolic Pulsed Wave Tissue Doppler Parameters and Both Invasive and Noninvasive Reperfusion Criteria in Patients with Acute Anterior Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Despite normal flow in the infarct-related artery after primary percutaneous coronary intervention, patients may not achieve adequate perfusion at the tissue level. We examined the applicability of pulsed wave tissue Doppler (PTD) in detection of successful myocardial reperfusion. In all, 24 patients with anterior infarction were enrolled. All patients underwent primary percutaneous coronary intervention. PTD was performed 2 days and 2 weeks after percutaneous coronary intervention, and recorded from 6 different locations at the mitral annular level. Peak systolic wave was determined and was related to various markers of reperfusion. Systolic PTD measurement in patients with myocardial blush grades 0 to 1 significantly deteriorated between second day and second week (6.5 +/- 1.1-5.3 +/- 1.1 for the anterior wall, and 6.2 +/- 1.3-5.3 +/- 1 for the anterior septum, P < .05 and P < .01, respectively). Systolic PTD parameters improved significantly in patients with myocardial blush grades 2 to 3 (6 +/- 1.5-7.2 +/- 2 for the anterior wall, and 5.4 +/- 1.1-7.1 +/- 1.6 for the anterior septum, P < .05 and P < .01, respectively). A significant relationship was observed between PTD and thrombolysis in myocardial infarction flow, S-T resolution, and creatine phosphokinase peaking. PTD recovery was highly sensitive and specific for the detection of left ventricular function recovery. We demonstrated a significant relationship between systolic PTD parameters and invasive and noninvasive markers of reperfusion. Larger studies are needed to confirm these results.

Reducing Myocardial Injury by Minimizing Imbalance between Oxygen Supply and Demand

The purpose of this study was to determine whether hemodynamic and pharmacologic factors can influence the extent and severity of myocardial necrosis produced by coronary occlusion. In 48 dogs, 10 to 14 epicardial leads were recorded on the anterior surface of the left ventricle in the distribution and vicinity of the site of occlusion of a branch of the left anterior descending coronary artery. The average S-T segment elevation for each animal was determined at 5-min intervals after occlusion. This elevation was used as an index of the presence and severity of myocardial ischemic injury. Isoproterenol, ouabain, glucagon, bretylium, and tachycardia given prior to a repeated occlusion each increased the severity and extent of ischemic injury, while propranolol decreased it. Elevation of arterial pressure with methoxamine reduced the occlusion-induced S-T segment elevation, and lowering of the mean arterial pressure by hemorrhage had the opposite effect. In 19 additional experiments, propranolol, isoproterenol, and alterations in arterial pressure produced similar alterations in S-T segment elevation when these interventions were applied as long as 3 hr after ligation. Myocardial creatine phosphokinase (CPK) activity determined 24 hr after coronary artery ligation correlated well with S-T segment elevation at the same sites recorded 15 min after ligation. Moreover, isoproterenol increased and propranolol decreased the area of depression of myocardial CPK activity. We conclude that the hemodynamic status and neurohumoral background at the time of coronary occlusion and for at least 3 hr thereafter can alter the extent and severity of myocardial ischemic injury and myocardial necrosis.

Verapamil reduces coronary endothelium damage and cardiomyocyte necrosis but not apoptosis after ischemia and reperfusion: ex-vivo study in rat hearts.

We tested the hypothesis of beneficial effects of the calcium-blocker verapamil in a model of ischemia-reperfusion, and investigated its effects against coronary microcirculation and cardiomyocyte apoptosis. Isolated working rat hearts were subjected to 15 min global ischemia and 22-180 min reperfusion in the presence or absence of verapamil (0.25 &mgr;M). We evaluated creatinephosphokinase (CK) in coronary effluent, heart weight changes, microvascular permeability (extravasation of fluoresceine-labeled albumin), ultrastructural alterations, and cardiomyocyte apoptosis (by 1.5% agarose gel electrophoresis and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling technique). In this model, 0.25 &mgr;M verapamil significantly reduced myocardial damage, CK release and vascular hyperpermeability, concomitant with a reduction in endothelial and cardiomyocyte lesions; on the contrary, 0.25 &mgr;M verapamil was unable to reduce cardiomyocyte apoptosis. In conclusion, in the absence of perfusing granulocytes, the acute administration of a pharmacologically relevant verapamil concentration reduces ischemia-reperfusion injury and prevents coronary endothelial cell and cardiomyocyte necrotic cell death but it is unable to reduce apoptotic cell death in isolated working rat hearts.

ST segment changes following retinal surgery

Study Objective: To describe the perioperative cardiac morbidity in adult patients undergoing retinal surgery using continuous Holter monitoring. Design: Prospective study. Setting: University hospital. Patients: 56 patients scheduled for elective retinal surgery with local anesthesia. Interventions: Patients were monitored continuously for 24 hours using a Holter recorder. Blood samples for creatine phosphokinase (CPK) and serum myocardial creatine phosphokinase (CPK-MB) were taken preoperatively and 24 hours postoperatively. The characteristics of myocardial ischemia were compared according to the number of risk factors for ischemic heart disease. Measurements and Main Results: The overall incidence of perioperative myocardial ischemia was high: 26.7% (n = 15). These patients exhibited 41 episodes of ischemia with mean ST segment change from baseline of 2.2 ± 0.7 mm. However, almost all (93.3%) ischemic episodes were silent. Patients with two risk factors or more had 77% more episodes of ischemia than patients with one risk factor (p < 0.005), and the duration of ischemia was 47 ± 22.5 minutes compared with 34.8 ± 27.5 minutes (p = NS). The first episode of ischemia occurred an average of 10 hours after surgery. No patient had intraoperative evidence of ischemia. Half of the ischemic episodes were associated with an increase in heart rate. No patient had evidence of acute myocardial infarction. Conclusion: Retinal surgery with local anesthesia is accompanied by a high incidence of postoperative myocardial ischemia. No negative outcome was correlated to the occurrence of postoperative myocardial ischemia. The significance of these findings has yet to be evaluated.

Association between Q-Wave Myocardial Infarction and Myocardial Creatine Phosphokinase Release after Elective Coronary Artery Bypass Graft Surgery

Association between Q-Wave Myocardial Infarction and Myocardial Creatine Phosphokinase Release after Elective Coronary Artery Bypass Graft Surgery

Transmural distribution of antioxidant defences and lipid peroxidation in the rabbit left ventricular myocardium

The left ventricular subendocardial and subepicardial layers of six perfused rabbit hearts were tested for enzymatic and non-enzymatic antioxidant defences and for lipid peroxidation. The subendocardium showed significantly lower catalase activity and contents of non-protein thiol compounds and vitamin E associated with a higher degree of lipid peroxidation. The activities of Cu,Zn- and Mn-superoxide dismutases, glutathione reductase, gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase showed no significant transmural differences, and Se-independent glutathione peroxidase activity was not detectable in either layer. Comparable results were observed in another group of six unperfused rabbit hearts. In five H2O2-perfused rabbit hearts, lipid peroxidation was higher, and myocardial creatine phosphokinase activity lower, in the subendocardium than in the subepicardium. In this group, only the subendocardium had significantly higher lipid peroxidation levels than the control hearts. Thus, a lower antioxidant capacity and a greater oxidative stress are present in the rabbit subendocardium. These findings could provide insight into the problem of subendocardial vulnerability to free radical-mediated processes, such as occurs in ischaemia-reperfusion injury.

G619, a dual thromboxane synthase inhibitor and thromboxane A2 receptor antagonist, reduces myocardial damage and polymorphonuclear leukocyte accumulation following coronary artery occlusion and reperfusion in rats.

We investigated the effect of G 619, a dual thromboxane synthase inhibitor and thromboxane A2 (TxA2) receptor antagonist, in pentobarbital-anaesthetized rats subjected to left main coronary artery ligation (1 h) followed by reperfusion (1 h; MI/R). Sham-operated rats were used as controls (sham MI/R). Survival rate, myocardial necrosis, myocardial myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation) and serum creatine phosphokinase (CPK) activity were studied. MI/R injury significantly reduced survival rate (45%), caused a marked myocardial necrosis, increased serum CPK activity (sham MI/R = 35 +/- 12 U/ml; MI/R = 205 +/- 13 U/ml) and produced an increase in myocardial MPO activity in the area at risk and in the necrotic area (6.3 +/- 0.5 and 6.6 +/- 0.9 U x 10(-3)/g tissue, respectively). The administration of G 619 significantly increased survival rate, lowered the area of necrosis, blunted the increase in serum CPK activity and reduced the increase in MPO activity in both the area at risk and the necrotic area. These data are consistent with an involvement of TxA2 in MI/R injury and suggest that G 619 may represent a novel therapeutic approach to the treatment of acute myocardial infarction.

Free radical scavenging is involved in the protective effect of l-propionyl-carnitine against ischemia-reperfusion injury of the heart

l-Propionyl-carnitine is known to improve the recovery of myocardial function and metabolic parameters reduced in the course of ischemia-reperfusion of the heart. The mechanism of this protective effect of l-propionyl-carnitine is not fully understood. The purpose of this study was to elucidate the effects of l-propionyl-carnitine in Langendorff perfused rat hearts subjected to 40 min of ischemia followed by 20 min of reperfusion. We tested the hypothesis that l-propionyl-carnitine suppresses generation of oxygen radicals and subsequent oxidative modification of myocardial proteins during reperfusion. Our data show that the protective effect of l-propionyl-carnitine in the course of ischemia-reperfusion is highly significant in terms both of mechanical properties of the heart (developed pressure) and of high-energy phosphates (ATP, creatine phosphate). Myocardial creatine phosphokinase (CPK) activity decreased in the course of the reperfusion period. The loss of CPK activity was partially prevented by l-propionyl-carnitine. Two other effects were observed when l-propionyl-carnitine was present in the perfusion solution: (i) the reperfusion-induced sharp increase in oxidative protein modification was completely prevented as detected by the formation of protein carbonyls, and (ii) generation of hydroxyl radicals was significantly inhibited as detected by the formation of the adducts with the spin trap 5,5-dimethyl-1-pyrroline-1-oxide. We conclude that the protective effect of l-propionyl-carnitine against ischemia-reperfusion injury of the heart is at least due in part to its ability to suppress the development of oxidative stress and free radical damage.

Effects of residual coronary stenosis on myocardial salvage after reperfusion in dogs.

In order to study the effects of residual stenosis on myocardial salvage, we created 99% coronary stenosis with or without contrast washout delay at reperfusion in six groups of dogs. In Group A (n = 8), the artery was occluded for 1h before being fully reperfused. In Group B (n = 9), the artery was occluded for 1h, then subjected to 6h of 99% stenosis without contrast washout delay. In Group C (n = 8), the artery was occluded for 1h, followed by 1 week of 99% stenosis without contrast washout delay. In Group D (n = 10), again the artery was occluded for 1h, then subjected to 6h of 99% stenosis with contrast washout delay. In Group E (n = 8), the artery was occluded for 7h, then fully reperfused for 1 week. Finally, in Group F (n = 8), the occlusion lasted for a full week. All dogs were sacrificed 1 week after occlusion. In Group A, myocardial creatine phosphokinase activity (CK) in the inner layer was 43.8 +/- 12.5% that of non-infarcted myocardium. Myocardial CK in Group B (46.5 +/- 7.4%) was little different but in Group C it dropped to 26.6 +/- 8.4%, suggesting that 99% residual stenosis is not deleterious if it is continued for 6h or less but that it will result in considerable depletion of myocardial CK, it is is sustained for 1 week. In Group D, myocardial CK dropped markedly to 11.3 +/- 3.7%, little different from that for either Group E (13.3 +/- 2.6%) or Group F (9.3 +/- 3.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardioprotective effects of nicorandil on calcium paradox‐induced injury

AbstractNicorandil, a new antianginal drug, exerts a coronary vasodilation effect by mechanisms different from either nitrates or slow‐channel Ca++ entry blockers. This agent has been demonstrated to increase membrane K+ conductance, elevate cyclic guanosine monophosphate (GMP) content, and depress Ca++ current kinetics in vascular smooth muscle cells. In the myocardium, however, the direct effects of the agent have not been elucidated. We examined whether or not nicorandil could antagonize myocardial injury in the Langendorff‐perfused chick heart induced by the Ca++ paradox. The Ca++ paradox was produced by 15 min of Ca++‐free perfusion, followed by 10 min of Ca++ reperfusion. Nicorandil was added to the perfusing solution only during the Ca++ reperfusion phase. In the Ca++ paradox hearts, the following were observed: (1) depression of myocardial creatine phosphokinase and adenosine triphosphate (ATP) contents; (2) elevations of myocardial H2O, Na+, and Ca++ contents; and (3) ultrastructural derangement, which included contraction bands, interstitial edema, and mitochondrial swelling. Nicorandil treatment significantly attenuated the histological perturbation and part of the biochemical alterations. The present study suggests that nicorandil partially protects the myocardium against the Ca++ paradox‐induced injury.

Involvement of vitamin D3 with cardiovascular function. III. Effects on physical and morphological properties

We have previously shown that depletion of vitamin D3 in rats results in a large increase in the contractile function of isolated hearts (R. E. Weishaar, J. Clin. Invest. 79: 1706-1712, 1987). To characterize the mechanism responsible for this increase, the effect of vitamin D3 depletion on key physical and morphological properties of cardiac muscle was examined. Depletion of vitamin D3 increased the heart weight/body weight ratio. This increase could neither be blocked by limiting hypocalcemia nor reversed by restoring increasing serum calcium levels. The cardiomegaly observed 9 wk after vitamin D3 depletion was not accompanied by an increase in myocardial water content or leakage of myocardial creatine phosphokinase and was not caused by myocardial cell hypertrophy. Histological examination of ventricular muscle from vitamin D3-deficient rats revealed a significant decrease in myofibrillar area and a significant increase in extracellular space. The increase in extracellular space was accompanied by a significant increase in myocardial collagen. Prevention of hypocalcemia in the vitamin D3-deficient rats did not prevent the increase in myocardial collagen. Such alterations in the physical and morphological properties of myocardial tissue might represent the basis for the change in myocardial contractile function that accompanies lengthy periods of vitamin D3 deficiency.

Regional myocardial blood flows during occlusion and reperfusion as measured by non-radioactive colored microsphere and their correlation with regional myocardial creatine phosphokinase release

Regional myocardial blood flows during occlusion and reperfusion as measured by non-radioactive colored microsphere and their correlation with regional myocardial creatine phosphokinase release

Effects of chronic administration of doxorubicin on myocardial creatine phosphokinase and antioxidant defenses and levels of lipid peroxidation in tissues and plasma of rats.

Tissue and plasma levels of thiobarbituric acid reactive substances (TBARS) were measured in rats treated chronically with doxorubicin. In addition, heart creatine phosphokinase and antioxidant defenses were examined. Male rats received doxorubicin (DXR) 2 mg/kg or vehicle weekly subcutaneously for 13 weeks and were sacrificed at 14 and 19 weeks, 1 and 6 weeks after the last dose, respectively. Histological evaluation in DXR-treated rats at 14 and 19 weeks found significant and progressive cardiac and renal lesions as compared to controls. Heart TBARS were unchanged from controls. Plasma and kidney levels of TBARS were elevated above controls at both 14 and 19 weeks. Lung levels of TBARS were significantly elevated above controls at 14 weeks. Liver levels of TBARS were elevated at 19 weeks. Heart creatine phosphokinase activity was significantly depressed from controls at both 14 and 19 weeks. Heart glutathione peroxidase and superoxide dismutase activities were unchanged from controls. Heart glutathione, glutathione reductase, glucose-6-phosphate dehydrogenase, and catalase were elevated above controls at both 14 and 19 weeks. The lack of change in heart TBARS suggests that changes in TBARS in other organs may be secondary processes. The depression of creatine phosphokinase suggests that levels of adenosine triphosphate may be insufficient to sustain the myocardial function and this may partly be responsible for DXR-induced cardiac myopathy.