Persistence of systolic coronary flow reversal predicts irreversible dysfunction after reperfused anterior myocardial infarction.

OBJECTIVE: To investigate serial assessments of systolic coronary flow reversal in the infarct related artery for predicting poor left ventricular functional recovery after reperfused acute myocardial infarction. SETTING: Regional hospital. PATIENTS AND METHODS: 49 patients with anterior acute myocardial infarction had transthoracic Doppler echocardiography to record coronary flow velocity in the left anterior descending coronary artery immediately after successful primary coronary angioplasty (day 0), and at 48 hours, one week, and three weeks. MAIN OUTCOME MEASURES: Coronary flow velocity at each time point; regional wall motion score index (RWMSI) at day 0 and at three weeks. Irreversible dysfunction was defined as a decrease in RWMSI to < 0.22. RESULTS: Measurements of coronary flow velocity could be made in 45 patients. Patients were divided into three groups: no systolic flow reversal (group 1, n = 27), systolic flow reversal observed only on day 0 (group 2, n = 8), and systolic flow reversal persisting until 48 hours (group 3, n = 10). Although baseline RWMSI was similar among the three groups, the value at three weeks was significantly higher in group 3 than in the other two groups. In predicting irreversible dysfunction, the persistence of systolic flow reversal up to 48 hours had a higher positive predictive value (100%) than the presence of systolic flow reversal on day 0 (67%, p < 0.04). The negative predictive value of systolic flow reversal at 48 hours (83%) was comparable in accuracy to the presence of systolic flow reversal on day 0 (85%, NS). CONCLUSIONS: In reperfused anterior acute myocardial infarction, serial assessment of coronary flow velocity in the left anterior descending coronary artery is feasible using transthoracic Doppler echocardiography, and the persistence of systolic flow reversal at 48 hours is a more specific marker of irreversible dysfunction than peak creatine kinase or diastolic deceleration time.

Differences in management and outcomes of acute myocardial infarction among four general hospitals in Japan.

OBJECTIVE: To ascertain the differences among hospitals in Japan in the management patterns and outcomes of patients with acute myocardial infarction (AMI). DESIGN: Retrospective cohort study by means of patient chart review. SETTING: Four tertiary-care teaching hospitals in Japan observed over a 1-year period. STUDY PARTICIPANTS: Consecutive patients (N=482) admitted for AMI. MAIN OUTCOME MEASURES: Clinical characteristics, rates of diagnostic and therapeutic procedures performed, cardiac complications, and length of stay. RESULTS: Patients' clinical characteristics differed significantly among the four hospitals in terms of age, gender, and prior cardiac history, but not in terms of comorbidity or infarct location. The frequency and type of diagnostic and therapeutic procedures were different, and in-hospital mortality varied (4-14%, P=0.022). Average length of hospital stay ranged from 15.8+/-12.6 days to 41.0+/-19.4 days (P=0.0001). After adjustment for the clinical characteristics, these differences remained significant among hospitals. CONCLUSION: Considerable differences in the management and outcomes of patients with AMI exist in Japan.

Management of patients with acute myocardial infarction at five academic medical centers: clinical characteristics, resource utilization, and outcome.

BACKGROUND: Although variability in management of cardiovascular syndromes has been demonstrated among regions, the extent to which variability exists among academic medical centers in different countries in uncertain. METHODS: This retrospective cohort study includes data on consecutive patients (n = 694) with acute myocardial infarction who were admitted to five teaching hospitals from different countries (84, Brigham and Women's Hospital, USA; 97, Iizuka Hospital, Japan; 64, Hospital de Clinicas de Porto Alegre, Brazil; 62, Universitätsklinikum Charité, Germany; and 387, Hôpital Cantonal Universitaire de Genève, Switzerland) during a one-year period. Data were collected via chart review on clinical characteristics, rates of diagnostic and therapeutic interventions, complications and mortality, length of stay, and one-year follow-up outcomes. RESULTS: Patients' clinical characteristics varied among these institutions, with the lowest prevalence of antero-septal myocardial infarction at the US hospital. The US hospital had the lowest rate of use of thrombolytic therapy and did not have the highest rate for any invasive procedure. Average length of stay ranged from 7.7 +/- 4.3 days in the US hospital to 47.2 +/- 27.9 days in the Japanese hospital. There were no differences in one-year mortality among the four institutions (4% to 8%, P = 0.881) for which data were available. CONCLUSIONS: In this nonrandom sample of academic medical centers, the use of aggressive therapies for acute myocardial infarction was at least as common at non-US as US hospitals. Length of stay was much shorter at the US hospital. Despite these variations in management, evidence for differences in outcomes at one year were not detected.

Effect of cilostazol, a novel anti-platelet drug, on restenosis after percutaneous transluminal coronary angioplasty.

The possible preventive effect of cilostazol, a novel anti-platelet drug, on restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) was examined. One hundred and two consecutive patients, who underwent successful PTCA, were followed for 3 to 6 months. To prevent restenosis, 46 patients (60 PTCA sites) were treated with cilostazol alone (200 mg/day) (cilostazol group) and the remaining 56 (61 PTCA sites) were treated with other anti-platelet drugs and/or warfarin potassium (control group). Restenosis was defined as a more than 50% loss of the initial gain of the coronary diameter achieved by PTCA. Cilostazol did not significantly reduce the patient or lesion restenosis rate; the patient restenosis rate was 32% in the control group and 22% in the cilostazol group (P = 0.24), and the lesion restenosis rate was 30% in the control group and 23% in the cilostazol group (P = 0.44). However, the lesion non-progression rate, which was defined as the incidence of lesions with either no change or regression of coronary stenosis at the PTCA site, was significantly greater with cilostazol (37%) than in the control group (16%) (p < 0.05). Although cilostazol failed to show a significant reduction in restenosis after PTCA, the present results suggest that a further trial with a larger number of patients is needed to confirm its usefulness.

Endothelial Gi protein expression is markedly low in human coronary microvessels.

Gi protein functionally mediates endothelium-dependent relaxations in large epicardial coronary arteries but not in small coronary arteries, which suggests a different involvement of Gi protein in the endothelium-dependent relaxations between large and small coronary arteries. We previously showed that endothelial Gi protein is present in human epicardial coronary artery. In the present study, we examined the expression of endothelial Gi protein in human coronary microvessels. Immunohistochemical staining with a specific antibody against human Gi protein was performed in intramyocardial coronary microvessels and vasa vasorum from 34 autopsy cases. The immunoreactive levels of the endothelial Gi protein were semiquantitated into four grades (none, 0; slight, +1; moderate, +2; high, +3), and the mean value of the ratings of all endothelial cells was then used as an index of the endothelial Gi protein expression of the vessel. The immunoreactive levels of the endothelial Gi protein were extremely low in intramyocardial coronary microvessels and in vasa vasorum, irrespective of the age of the patients, the presence or absence of coronary risk factors, or the influence of medical treatments. These results may therefore explain in part why endothelium-dependent relaxations in coronary microvessels are not functionally mediated by Gi protein.

Granulocyte activation in restenosis after percutaneous transluminal coronary angioplasty.

To examine whether or not granulocyte activation is involved in restenosis after percutaneous transluminal coronary angioplasty (PTCA), we prospectively followed the time course of the plasma level of granulocyte elastase, which is an index of granulocyte activation, before and after successful angioplasty in 43 consecutive patients. Restenosis was defined as a more than 50% loss of the initial gain in the coronary diameter achieved by PTCA with more than a 50% resultant stenosis in the follow-up coronary arteriography performed 3 months after PTCA. There was no difference in the level of granulocyte elastase between the 2 groups with (n = 15) and without (n = 28) restenosis before, the day after and 1 month after PTCA. However, 3 months after PTCA, the level of granulocyte elastase was significantly higher in the group with restenosis than in that without restenosis (171 +/- 13 vs 147 +/- 6 mg/l, P < 0.05). The level of granulocyte elastase at 3 months after PTCA also correlated significantly with the percent luminal stenosis at the angioplasty site (P < 0.05). These results suggest that granulocyte activation may be involved in restenosis after PTCA.

Endothelial Gi protein in human coronary arteries.

Endothelium-dependent relaxations mediated by Gi protein are prominently impaired in atherosclerotic coronary arteries. However, it remains to be determined whether the expression of endothelial Gi protein per se is reduced in coronary atherosclerosis. Thus, in the present study the expression of endothelial Gi protein was examined by immunohistochemical staining using a specific antibody against human Gi protein (alpha-subunits of Gi-1 and Gi-2 proteins) in the proximal segment of the left anterior descending coronary arteries (segment 6) from 40 consecutive autopsy cases. The immunoreactive level of the Gi protein was semi-quantitated in four grades (none, 0; slight, +; moderate, +2; high, +3) and the mean value of the ratings of all endothelial cells was used as an index of the endothelial Gi protein expression of the artery. The immunoreactive level of the Gi protein in human coronary arteries was significantly reduced with ageing and extent of coronary atherosclerosis (both P < 0.05), and was lower in patients with than in those without hypertension (P < 0.01) or hyperlipidaemia (P < 0.05). In addition, the level was significantly lower in the eccentric portions than in the concentric ones in each atherosclerotic coronary artery (P < 0.0001). These alterations in the immunoreactive level of endothelial Gi protein in human coronary arteries may explain, in part, why Gi protein-mediated, endothelium-dependent relaxations are prominently impaired in atherosclerosis.

Intracellular magnesium deficiency in acute myocardial infarction.

It has been hypothesized that intracellular magnesium deficiency is a pathogenetic factor in acute myocardial infarction. This study examined the time course of changes in the erythrocyte magnesium concentration and the correlation between the erythrocyte magnesium concentration and the severity of acute myocardial infarction in 49 consecutive patients with transmural acute myocardial infarction. The data were compared with results from 20 control patients without ischemic heart disease. The erythrocyte magnesium concentration (mg/dl) decreased significantly during the acute phase of the infarction (4.86 +/- 0.09 on day 1, 4.89 +/- 0.10 on day 2 and 4.86 +/- 0.10 on day 3 versus 5.26 +/- 0.19 for controls, all P < 0.05) and then normalized gradually to 5.25 +/- 0.10 on day 28. The serum magnesium concentration (mg/dl) also decreased significantly during the acute phase of the infarction (1.93 +/- 0.04 on day 1 and 2.11 +/- 0.03 on day 2 versus 2.26 +/- 0.08 for controls, all P < 0.05), before recovering to 2.28 +/- 0.06 on day 28. There were significant correlations between the erythrocyte magnesium concentration on day 1 and maximal values of serum cardiac enzymes (r = -0.30 for creatine kinase, r = -0.34 for glutamic oxaloacetic transaminase and r = -0.57 for lactate dehydrogenase, all P < 0.05). Moreover, the erythrocyte magnesium concentration was significantly lower in patients with (4.32 +/- 0.08 mg/dl, n = 13) than in those without (5.06 +/- 0.09 mg/dl, n = 36, P < 0.0001) serious arrhythmias. These data indicate that intracellular magnesium deficiency is involved in the acute phase of myocardial infarction.

Alcohol-induced sinus bradycardia and hypotension in patients with syncope.

We observed 2 cases of repeated episodes of syncope after alcohol ingestion. Both patients were light drinkers and had carotid sinus hypersensitivity. In both cases, alcohol loading tests repeatedly induced sinus bradycardia and hypotension 1.0-1.5 hours after drinking alcohol. Atropine was effective in improving symptoms. A loading test using a glucose solution of equivalent osmolarity and volume was negative. Acute alcohol ingestion usually increases heart rate with variable effects on blood pressure. However, our 2 cases exhibited unusual alcohol-induced sinus bradycardia and hypotension, suggesting a paradoxical increase in parasympathetic activity and/or decrease in sympathetic activity.

Impaired blood pressure response to exercise in patients with coronary artery disease: possible contribution of attenuated reflex vasoconstriction in non-exercising muscles.

Eighteen patients with coronary artery disease were divided into two groups according to whether their blood pressure decreased (eight, group 1) or increased (10, group 2) in response to treadmill exercise testing. Age and the extent and distribution of coronary artery disease were similar in the two groups. At rest, blood pressure, pulmonary artery wedge pressure, cardiac index, forearm vascular resistance, and oxygen consumption were similar in the two groups. During supine leg exercise on a bicycle ergometer mean blood pressure increased in group 2 but did not change in group 1. Increases in cardiac index, pulmonary artery wedge pressure, and oxygen consumption during leg exercise were not significantly different in the two groups but forearm vascular resistance increased less in group 1 than in group 2. There was a positive correlation between the magnitude of the change in mean blood pressure and change in forearm vascular resistance during leg exercise. The impaired response of blood pressure to leg exercise in group 1 was not the result of a failure of the cardiac index to increase. The results suggest the possibility that attenuation of reflex vasoconstriction in non-exercising muscles may contribute to the impaired response of blood pressure to exercise in patients with coronary artery disease.

Biphasic response of coronary arterial diameter to intracoronary ergonovine.

This report presents a case of paradoxical coronary arterial dilation induced by intracoronary ergonovine. When compared with the control angiogram, the right coronary artery obviously dilated with selective, intracoronary administration of cumulative doses of 5 micrograms and 15 micrograms ergonovine without concomitant hemodynamic changes. Additional intracoronary infusion of 35 micrograms ergonovine into the right coronary artery inversely increased vascular tone of the vessel associated with a focal hyperconstriction. Such a biphasic response of arterial diameter to intracoronary ergonovine was also observed in the left coronary artery, but the degree of dilation was much smaller.

Prevention of vasospastic angina by alcohol ingestion: report of 2 cases.

The authors report 2 patients with vasospastic angina in whom alcohol ingestion was effective in preventing angina. Coronary angiography revealed no organic coronary stenosis but demonstrated coronary artery spasm during angina attacks. In 1 patient, alcohol ingestion every six hours completely suppressed frequent spontaneous angina. In the other patient, alcohol ingestion markedly prolonged the duration of the exercise on treadmill testing by preventing exercise-induced coronary spasm.

Cimetidine induces coronary artery spasm in patients with vasospastic angina.

We have previously reported that cimetidine, a histamine H2-receptor blocker, augments the histamine-induced coronary vasoconstriction at the site of spastic segments in the atherosclerotic coronary arteries of swine. To elucidate whether cimetidine has a coronary vasoconstrictive effect in humans, 14 patients with vasospastic angina (group 1) and 14 controls with atypical chest pain (group 2) were examined angiographically. Nitroglycerin-effective spontaneous angina with electrocardiographic ST-T changes and ergonovine-induced coronary artery spasm were confirmed in group 1, but not in group 2. Cimetidine was administered intravenously in a dose of 200 mg. Cimetidine induced coronary artery spasm in 4 patients in group 1 but none in group 2(29% vs. 0%, p less than 0.01). The extent of coronary vasoconstriction induced by cimetidine was greater at the site of spastic coronary segments than that at the site of non-spastic segments in group 1 or all segments in group 2 [14% vs. 4%, (p less than 0.01) or 14% vs. 2%, (p less than 0.01)] as well as the extent of ergonovine-induced coronary vasoconstriction [46% vs. 14%, (p less than 0.01) or 46% vs. 14%, (p less than 0.01)] and nitroglycerin-induced coronary vasodilatation [58% vs. 25%, (p less than 0.01) or 58% vs. 17%, (p less than 0.01)]. As it was suggested that cimetidine has potential vasoconstrictive effects in patients with coronary artery spasm, it should be administered with caution in patients with the vasospastic angina pectoris.

Effort angina without coronary obstruction in a patient with Takayasu's aortitis: a case report.

Angina occurring in patients with Takayasu's aortitis is attributed to the narrowing of the coronary ostium and/or aortic regurgitation. We treated a patient with Takayasu's aortitis with effort angina, in whom there was no obstruction of the ostium or aortic regurgitation. Treadmill exercise stress test revealed significant ST depression in leads V4-6, II, III and aVF with chest pain. Examinations of lactate in coronary sinus as well as arterial blood suggested the occurrence of myocardial ischemia during atrial pacing. The DPTI/TTI index was decreased and the left ventricular end-diastolic pressure was increased during angina. It is considered that the reduced coronary perfusion pressure resulted from a low diastolic aortic pressure and the elevated left ventricular end-diastolic pressure decreased the DPTI/TTI index and contributed to the development of subendocardial ischemia.

The protective effects of nifedipine in the isolated cat heart.

The calcium channel blocking agent, nifedipine, was studied during global ischemia and reperfusion in isolated cat hearts perfused with Krebs-Henseleit solution. Nifedipine was added to the reservoir and 0.1 micrograms/ml perfusate/hr of nifedipine was infused for 150 min. After 120 min of ischemia (flow at 1% of control), the heart was reperfused with nifedipine-containing perfusate for 20 min and with nifedipine-free perfusate for an additional 25 min. In control hearts, nifedipine significantly reduced the percent free activity of the lysosomal protease cathepsin D (P less than 0.01). In ischemic hearts, nifedipine protected against the increased myocardial tissue edema (P less than 0.01), the increased percent free cathepsin D activity (P less than 0.02) and the postreperfusion increased creatine kinase activity (P less than 0.01). Thus, nifedipine showed membrane stabilizing and cytoprotective activities in myocardial cells, after postischemic reperfusion. These data suggest that calcium ions contribute to the lysosome labilization and cytoplasmic enzyme leakage observed in ischemia and reperfusion, and that calcium channel blockade may protect myocardial cellular integrity during both ischemia and reperfusion.

Two-dimensional echocardiographic demonstration of so-called aneurysm of the membranous ventricular septum in adults--value of combined "manual scanning".

Using two-dimensional (2-D) echocardiography we evaluated the applicability of the left ventricular (LV) short axis view combined with manual scanning technique for the detection and evaluation of aneurysms of the membranous ventricular septum (AMS). In 12 patients with angiographically proven AMS, we recorded from the left sternal border the short axis view of the left ventricle continuously displayed from the aortic to the ventricular level by tilting the transducer manually along the LV long axis plane. We then compared the detectability of AMS by this method with that by other standard fixed 2-D echocardiographic views. This method proved to be best for the detection of AMS (12/12), followed by an apical four-chamber view (10/12), a parasternal LV long axis view (8/12) and an apical two-chamber (2/12) view. For the detection of AMS and for three-dimensional evaluation of the structure of the AMS and the original orifice of ventricular septal defect the method was shown to be clinically applicable.

Salutary actions of thromboxane synthetase inhibition during global myocardial ischemia.

Isolated cat hearts were perfused with blood-free Krebs-Henseleit solution for 165 min. Ischemia was induced by reducing perfusion to 0.02 ml/min/g wet heart weight for 2 h followed by reperfusion at controls flows for 30 min. Hearts perfused with the thromboxane synthetase inhibitor OKY-1581 at concentrations of 5 X 10(-6) M were spared from the increases in circulating thromboxane B2 occurring in untreated ischemic hearts. After reperfusion, cardiac contractile force increased to a higher level in OKY-1581 treated hearts. This was associated with a lower coronary vascular resistance than in untreated ischemic hearts. OKY-1581 treated ischemic hearts exhibited lower perfusate and higher myocardial creatine kinase (CK) activity than untreated ischemic hearts, indicative of preservation of cellular integrity. Also, OKY-1581 treated ischemic hearts showed improved lysosomal stability as evidenced by a lower tissue percent free cathepsin D activity than untreated ischemic hearts. These results are consistent with a significant role of thromboxanes in the propagation of myocardial cellular damage during ischemia.

Protective actions of dexamethasone in acute cerebral ischemia.

The effects of glucocorticoids on cerebral integrity during cerebral ischemia (CI) are not clear. We induced CI in rabbits by occlusion of the left external carotid artery and injection of sodium arachidonate (NaAr) in the left internal carotid artery. We investigated the effect of dexamethasone (DEXA) on NaAr--induced CI. We examined four groups: a) Sham CI, b) CI, c) CI + Dopamine (80 micrograms/kg/min), and d) CI + Dopamine + DEXA (6 mg/kg). The EEG was recorded over the hemisphere injected with NaAr. After 240 min of observation, the brain was sampled to measure water content and to examine the cerebral vasculature microscopically. The dose of NaAr was similar in all ischemic groups (ie, 0.45 to 0.50 mg). In both CI, and CI + Dopamine groups, the EEG became flat in all 13 rabbits. Moreover, the water content of the left hemisphere increased (P less than 0.01 vs Sham CI), but that of the right side only slightly. In the CI + Dopamine + DEXA group, only one rabbit out of seven showed a flat EEG. Water content of the left side increased slightly and that of the right side not at all. Microscopic examination of the brain showed obstruction of cerebral arterioles in the left hemisphere in rabbits given NaAr. Thus, DEXA protects the brain from edema induced by NaAr, when blood pressure is maintained by dopamine. This is associated with preservation of cerebral electrical activity. However, dopamine alone was unable to preserve the EEG or protect against edema formation during cerebral ischemia.

Cardiac effects of prostaglandins during global ischemia in isolated perfused cat hearts.

Prostaglandin E1,PGD2, and 16,16 dimethyl prostaglandin E2 were studied in an isolated perfused cat heart preparation during normal conditions and in myocardial ischemia. Under ischemic perfusion, prostaglandin E1 showed some protective action on the release of creatine kinase into perfusate during ischemia, but none of the prostaglandins studied prevented increases in perfusate creatine kinase after reperfusion. Prostaglandin E1 also showed significant membrane stabilizing activity reducing the rate of lysosomal hydrolase release from cat liver lysosomes. Prostaglandin E1 may be beneficial in myocardial ischemia due to its membrane stabilizing action and perhaps to other effects but it did not exert significant protective effects on reperfusion injury of the ischemic myocardium under conditions of these experiments.