Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were performed to determine whether an alteration in coronary vascular resistance and a reduction in the reflow phenomenon occurred in the blood-perfused, heparinized canine heart after various periods of myocaridal ischemia. Regional myocardial blood flow was measured with radioactive microspheres. Proximal left anterior descending coronary artery blood flow was measured with a periarterial flow transducer. Reduced reflow to the ischemic portion of the left ventricle and increased resistance in the left anterior descending coronary artery were present after 120 minutes of myocardial ischemia. The reduction in reflow was specific to the subendocardium of the ischemic area. Saline and isosorbide dinitrate (Isordi) did not prevent the increase in coronary vascular resistance or the significant reduction in reflow to the subendocardial portion of the ischemic area. Hypertonic mannitol given so as to increase serum osmolality 40 mosmoles/kg prevented the increase in coronary vascular resistance and modified the reduction in the reflow phenomenon to the subendocardial portion of the ischemic area. Thus, both an increase in coronary vascular resistance and a significant reduction in reflow to the subendocardial portion of the ischemic area occur in the canine heart after 120 minutes of myocardial ischemia. Moreover, the increase in coronary vascular resistance can be prevented and the reduction in reflow to the subendocardial portion of the ischemic area can be modified by the administration of hypertonic mannitol.
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PMID:Reduced myocardial reflow and increased coronary vascular resistance following prolonged myocardial ischemia in the dog. 113 70

Cardiovascular disease has been the leading cause of death since 1946 in Japan. In this paper, the relationship between mortality and nutritional factors was analyzed by 12 different regions in Japan during the period 1966-1985. Data in the Reports of the National Nutritional Survey in Japan were used as the nutritional factors, and calculation was made of age-adjusted mortality from ischemic heart disease (IHD), cerebral hemorrhage (CH) and cerebral infarction (CI). The results obtained were as follows: 1. Correlation coefficients were calculated based on the average value of 20 years in each 12 different regions. Correlation coefficients between the mortality from IHD and intake of total fat and n3-polyunsaturated fatty acids were positively significant for both sexes. Between the mortality from CH and vegetable protein and salt, they were positively significant (p < 0.01) while cholesterol was negatively significant (p < 0.01). Between the mortality from CI and vegetable protein, salt and carbohydrate, they were positively significant (p < 0.01). 2. Correlation coefficients between slopes of CH and slopes of nutrients intakes, indicated cholesterol to be negatively significant (p < 0.05) for women from 1966-1970, and salt to be positively significant for men (p < 0.01) and women (p < 0.05) from 1974-1985. In the period 1966-1970, the correlation coefficient between slopes of IHD and those of Keys' factor was positively significant (p < 0.05) for women. 3. To clarify changes in the relationship between mortality and nutrients, correlation coefficients were calculated each year from 1966 to 1985. Significant positive correlation coefficients for IHD were found with animal protein and saturated fat starting from about 1975. Salt was associated with IHD in the 1960s but not following 1970. Those of nutrients for CH and CI did not change markedly during 18 years. 4. Multiple regression analysis with intake of salt and Keys' factor indicated that the influence of salt on cardiovascular disease to decreased and that that of low serum cholesterol on CH declined. Multiple correlation coefficients with salt and Keys' factor decreased for IHD (men) and CH (women).
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PMID:[Changes of nutritional factors related to regional differences in the mortality of cardiovascular disease between 1966 and 1985 in Japan]. 128 58

Earlier studies have demonstrated an improvement in the recovery of the regional myocardial function after reversible myocardial ischemia when dogs were treated with superoxide dismutase (SOD) + catalase (CAT). In all these studies, drug administration was started prior to the ischemic period. The aim of this study was to investigate the effects of SOD and CAT on the recovery of the regional contractile function in anesthetized beagle dogs when the drugs were administered at the time of reperfusion. The animals were subjected to 20 min of left coronary artery occlusion followed by 3 h reperfusion. The regional myocardial contractile function, measured as subendocardial segment shortening (SS, sonomicrometry) decreased to below zero and the regional blood flow in the ischemic subendocardium was reduced to about 5% of pre-ischemic values during the coronary artery occlusion period. The size of the occluded bed was similar in the two groups. Saline (n = 8) or SOD (10 mg/kg) + CAT (3.4 mg/kg) (n = 8) were infused into the left atrium from 2.5 min prior to until 20 min after the start of reperfusion. The peak plasma level of SOD was 102 +/- 15 mg/l at 20 min reperfusion. There were no significant differences in the arterial blood pressure, cardiac contractile function and regional blood flow between the two groups at any time during the experiment. During reperfusion in the dogs given vehicle, SS recovered to 48 +/- 7% (mean +/- SEM) after the first hour of reperfusion, and to 51 +/- 6% of pre-ischemic values after 3 h of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Superoxide dismutase and catalase do not improve recovery of regional myocardial contractile function when given at the time of reperfusion after reversible regional ischemia in anesthetized dogs. 177 87

The aim of this study was to differentiate myocardial reperfusion injury from that of ischemia. We assessed the role of the myocardial adenosine 5'-triphosphate (ATP) catabolites, hypoxanthine and xanthine, generated during ischemia and the early phase of reperfusion, in reperfusion injury by modulating adenosine transport and metabolism with specific metabolic inhibitors. This was followed by intracoronary infusion of exogenous hypoxanthine and xanthine. Twenty-four dogs instrumented with minor-axis piezoelectric crystals and intraventricular pressure transducers were subjected to 30 minutes of normothermic global myocardial ischemia and 60 minutes of reperfusion. In Group 1 (n = 7), normal saline was infused into the cardiopulmonary bypass reservior before ischemia and before reperfusion. Saline solution containing 25 microM p-nitrobenzylthioinosine (NBMPR) and 100 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) was infused in Group 2 (n = 10) dogs. Group 3 (n = 7) dogs were treated exactly like those in Group 2 except, at the end of the ischemic period and immediately before releasing the cross-clamp, a solution of EHNA-NBMPR containing 100 microM hypoxanthine and 100 microM xanthine was infused into the aortic root. Left ventricular performance and myocardial adenine nucleotide pool intermediates were determined before and after ischemia. ATP was depleted by about 50% (p less than 0.05 vs. preischemia) in all groups after 30 minutes of ischemia. Inosine was the major ATP catabolite (9.29 +/- 1.2 nmol/mg protein) in Group 1, while adenosine (9.91 +/- 0.7 nmol/mg protein) was the major metabolite in EHNA-NBMPR-treated dogs (Groups 2 and 3). Hypoxanthine levels were fivefold more in Group 1 compared with Groups 2 and 3 (p less than 0.05). Left ventricular performance in Group 1 decreased from 76.8 +/- 7.6 to 42.9 +/- 9.8 and 52.3 +/- 8.4 dynes/cm2 x 10(3) (p less than 0.05), while myocardial ATP decreased from 30.9 +/- 2.2 to 17.2 +/- 1.0 and 16.5 +/- 1.0 nmol/mg protein during 30 and 60 minutes of reperfusion, respectively (p less than 0.05 vs. preischemia). Ventricular function in Group 2 dogs completely recovered within 30 minutes of reperfusion, and myocardial ATP recovered to the preischemic level at 60 minutes of reperfusion. In Group 3, left ventricular performance was depressed by 39% and 30% during 30 and 60 minutes of reperfusion (p less than 0.05), respectively, and myocardial ATP did not recover during reperfusion despite a significant intramyocardial adenosine accumulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Myocardial reperfusion injury. Role of myocardial hypoxanthine and xanthine in free radical-mediated reperfusion injury. 318 Apr 2

The thrombolytic and hemodynamic properties of intracoronary streptokinase (SK) application were studied in an in-vivo canine model with left circumflex coronary artery thrombosis, initiated by electrical stimulation (150 microA, DC for 6 h) of the artery's intima via an implanted silver wire. In pentobarbital-anesthetized, open-chest dogs acute myocardial ischemia was determined by a dehydrogenase-dependent staining of the coronary artery perfusion area. Thrombus weight was determined post-mortem. Saline-treated control animals developed coronary thrombosis after 3.1 +/- 0.4 h of stimulation. Thrombus weight was 64 +/- 3.1 mg. Acute infarct volume was 32 +/- 3.1% of total left ventricle, and 53 +/- 6.2% of the coronary artery risk region for infarction. At occlusive thrombosis, blood pressure, ventricular pressure and the LV dP/dtmax fell significantly, whereas heart rate and the end-diastolic filling pressure increased. Severe ST-segment elevation and loss of R wave voltage indicated myocardial ischemia. At 20 min into thrombotic vessel occlusion, 2,000 IU/min SK were infused by way of a Sones-catheter advanced to the thrombus. Coronary thrombosis consistently lysed after 12 +/- 0.7 min of SK infusion, and coronary blood flow as well as hemodynamics were restored. Only minor acute infarction was found indicating viability of ischemic jeopardized myocardium. In another group, the continuous SK-infusion (20 IU/kg/min) concomitant with electrical vessel stimulation prevented coronary thrombosis and acute ischemia, and no significant hemodynamic alterations were noted. These results indicate that intracoronary SK-infusion can lyse acute thrombosis as sequel of electrical stimulation. This prevents development of acute myocardial infarction. Continuous SK-infusion can completely prevent coronary thrombosis in response to intimal injury.
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PMID:Thrombolytic effects of intracoronary streptokinase on canine coronary artery thrombosis. 673 17

We wished to determine, using a novel specific antagonist of BK2, HOE 140, (a) if the angiotensin-converting enzyme (ACE) inhibitor, ramiprilat, reduces myocardial infarct size in a well-established animal model of ischemia/reperfusion with minimal coronary collateralization, and (b) if the reduction in myocardial infarct size occurred through a bradykinin-dependent mechanism Saline vehicle, ramiprilat, HOE 140, or ramiprilat plus HOE 140 (n = 6 each group), was administered intravenously (i.v.) in intact animal preparations of experimentally induced acute myocardial ischemia. Anesthetized, open-chest rabbits were instrumented for measurement of systemic hemodynamics and left ventricular pressure (LVP), from which LV + dP/dtmax was derived. Animals were subjected to 30-min left main coronary artery occlusion (marginal branch) followed by 2-h reperfusion. Ramiprilat (50 micrograms/kg) or saline was administered before reperfusion, and rabbits receiving HOE 140 were pretreated before occlusion (1 microgram/kg). In separate duration of action experiments (n = 6 each group), the above doses of ramiprilat or HOE 140 had significant vascular antagonism of sufficient duration against serial challenge with angiotensin I (AI) or bradykinin, respectively. After reperfusion, myocardial infarct size (IS) was determined by tetrazolium staining and expressed as a percentage of area at risk (AR). IS/AR% was significantly reduced in rabbits that received ramiprilat (20 +/- 6%, p < 0.05) as compared with those that received saline (41 +/- 6%), ramiprilat plus HOE 140 (47 +/- 2%), or HOE 140 alone (43 +/- 4%, mean +/- SEM). AR as a percentage of total LV mass was not different between any of the four treatment groups. Tachycardia was observed during early reperfusion in each group treated with ramiprilat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction of myocardial infarct size in rabbits by ramiprilat: reversal by the bradykinin antagonist HOE 140. 768 28

The purpose of this study was to investigate the effects of lidocaine and diltiazem on ventricular tachyarrhythmia and dispersion of conduction during severe myocardial ischemia in dogs. Myocardial ischemia was produced by a 10-min occlusion of the left anterior descending artery by the retrograde blood flow technique. Saline, lidocaine, and diltiazem were infused intravenously before and during occlusion in groups A (n = 16), B (n = 22) and C (n = 13), respectively. The incidence of ventricular tachycardia (VT) consisting of ten or more VPC was 19% in group A, 73% in group B and 31% in group C (A vs. B, P < 0.01), and that of ventricular fibrillation (VF) was 31%, 64%, and 15%, respectively (A vs. B, P < 0.05). The time of the onset of VT preceding VF was shorter in group B than in group A (207.9 +/- 13.9 vs. 353.2 +/- 70.7 sec, P < 0.05). The time taken to reach maximal dispersion of conduction delay in the epicardium was shorter in group B than in group A (192.1 +/- 11.9 vs. 337.5 +/- 38.2 sec, P < 0.01), and the dispersion of conduction delay in the intramyocardial layers was smaller in group B than in group A (229.9 +/- 24.5 vs. 360.0 +/- 35.6 sec, P < 0.01). The time taken to reach maximal dispersion of conduction delay in the endocardium was greater in group C than in group A (400.8 +/- 38.8 vs. 274.4 +/- 23.9 sec, P < 0.01). However, there were no significant differences among the three groups with regard to the maximal dispersion of conduction delay in the epicardium, in the endocardium, or intramyocardial layer. These results suggest that lidocaine increased ventricular tachyarrhythmia due to an acute increase in dispersion of conduction in the epicardium and intramural layer, and that diltiazem was not effective in preventing ventricular tachyarrhythmia and did not affect the dispersion of conduction in the epicardium or intramural layer despite improvement in the endocardium.
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PMID:Effects of lidocaine and diltiazem on ventricular tachyarrhythmia and dispersion of conduction during severe myocardial ischemia in canine hearts. 943 76

Essential hypertensive patients with left ventricular hypertrophy (LVH) increase their mortality rates due to all cardiovascular diseases from 3 to 10 times more than hypertensives without signs of cardiac hypertrophy. LVH modifies the equilibrium between the oxygen supply and demand by the myocardium. The coronary reserve is appreciably reduced in hypertensives with LVH even in the absence of any stenosis of coronary arteries. Thus, in patients with normal coronary angiogram, a predisposition toward myocardial ischemia already exists. This process has been associated with the increased incidence of ventricular arrhythmias in essential hypertensives with LVH, what could be linked to the increasing risk of sudden death in these patients. In addition to hemodynamic factors (pressure and volume overload) several non-hemodynamic factors have been involved in the pathogenesis of LVH in hypertension. LVH would develop in subjects with a particular genetic substrate by the overlap of high blood pressure values and several factors linked to the adrenergic system, the renin-angiotensin-aldosterone system, other vasoactive substances, and growth factors. It has been previously reported that NaCl ingestion is a powerful determinant of left ventricular hypertrophy in patients with essential hypertension. Furthermore, a relationship between left ventricular mass and abnormalities in intracellular Na+ or transmembrane Na+ transport has been observed in several studies. Salt-sensitive hypertensive subjects seem to exhibit an increased risk in terms of cardiovascular morbidity. We and others have observed a higher left ventricular mass, an increased albumin excretion rate and a worse lipid profile in salt-sensitive compared with salt-resistant patients. The increase in LVMI in salt-sensitive patients is mainly due to the increase in septal and posterior wall thickness, with normal diastolic diameter, suggesting that myocardial growth in these patients is not volume-dependent. The mechanism of this structural cardiac adaptation is not completely understood. Nevertheless, it is known that salt-sensitive and salt-resistant hypertensive patients differ in some adaptive responses to changes in dietary salt intake. Among them, the renin-aldosterone axis, the sympathetic nervous system and the intracellular ion composition could play a role in the development of myocardial growth. In conclusion, salt-sensitive hypertensive patients exhibited an increased LVMI and a worse lipid profile, compared with salt-resistant hypertensives, even at the same level of blood pressure. These characteristics may confer to salt-sensitive patients an increased risk in terms of cardiovascular morbidity and mortality.
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PMID:Salt sensitivity and left ventricular hypertrophy. 943 15

Gestational hypertension and malnutrition are associated with hypertension and ischemic heart disease in the adult human. The impact of the gestational environment on the adult blood pressure in two well-characterized genetically homogeneous rat strains, the hypertensive SS/jr and normotensive SR/jr, was studied by cross-fostering within 6 hours of birth and by embryo transplantation with the recipient dam nursing the transplanted pups. Systolic blood pressure (BP) was measured by tail-cuff plethysmography twice a week after the age of 7 weeks. The lactational environment (cross-fostering) had no effect on blood pressure. Embryo transfer between like strains had no effect on the development of hypertension, nor did the BP of R transferred to S (RetS) differ from that of normal R or RetR. At 7 weeks of age, the BP of SetR was significantly lower than that of S or SetS (P<.01) and was similar to that of RetR and R. With age, the blood pressures of the S, SetS and SetR increased at approximately the same rate but from a significantly different baseline. Salt-sensitivity in the S and resistance in the R were not altered. The protective effect of the R gestational environment on SetR female BP was abrogated during whelping and lactation. Embryo transfer and cross-fostering did not alter the weight of rats older than 7 weeks. Because the BP of the R dams were significantly lower than that of the S dams, these studies do not distinguish between the effects of the R dams' lower blood pressure per se and hormonal influences of the R uterus on the S blood pressure phenotype.
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PMID:Modulation of blood pressure in the Dahl SS/jr rat by embryo transfer. 945 59

Neutrophils may contribute to myocardial ischemia/reperfusion (I/R) injury by generating reactive oxygen intermediates (ROIs). ROIs activate nuclear factor (NF)-kappaB, which regulates genes for cytokines with negative inotropic effects (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha). We investigated the impact of neutrophil depletion on NF-kappaB DNA binding activity, and expression of these cytokines during myocardial I/R injury. Male WKY rats (n = 28) received a single dose of antineutrophil antiserum (i/v). Twenty two hours later, when the peripheral blood neutrophil counts were profoundly decreased (94% reduction), the animals underwent 15 min of left anterior descending coronary artery ligation followed by reperfusion for 0.25, 0.5, 1, 2, 3, and 6 h (n = 4/group). Saline-treated animals underwent a similar protocol, and served as controls (n = 28, 4/group). Neutrophil accumulation, defined by myeloperoxidase activity, was present in controls, but not in anti-PMN antisera-treated animals (at least p <0.05 at 1, 2, 3, and 6 h R). Despite this difference, in both saline- and antiserum-treated animals, the GSH levels were very similar and fell significantly (p < 0.0001) at 15 min R; the levels increased gradually over time. In contrast, GSSG levels rose at 15 and 30 min R (p < 0.05), and declined thereafter. NF-kappaB DNA binding activity increased in both groups at 15 min and again at 3 h of R. Both NF-kappaBp50 and p65 subunits were detected by supershift assay. In saline-injected controls both mRNA and protein for IL-1beta, IL-6, and TNF-alpha were detected at 1 h R; levels remained high until 3 h, then fell (except IL-6, which was elevated at 6 h). In neutropenic animals, however, a significant decrease in mRNA (at least 1.7-fold, p < 0.05) as well as protein levels (at least 2. 3-fold, p < 0.01) for all three cytokines was observed. Thus, while neutrophils had minimal effects on oxidative stress (GSH/GSSG) and oxidative stress-responsive NF-kappaB activity, they contributed significantly to myocardial cytokine expression.
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PMID:Induction of nuclear factor kappaB but not kappaB-responsive cytokine expression during myocardial reperfusion injury after neutropenia. 1093 53


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