Enrico Orsini

Beneficial Effects of Intracoronary Adenosine as an Adjunct to Primary Angioplasty in Acute Myocardial Infarction

BACKGROUNDnThe benefits of vessel recanalization in acute myocardial infarction (AMI) are limited by reperfusion damage. In animal models, adenosine limits reperfusion injury, reducing infarct size and improving ventricular function. The aim of this study was to evaluate the safety and feasibility of adenosine adjunct to primary PTCA in AMI.nnnMETHODS AND RESULTSnFifty-four AMI patients undergoing primary PTCA were randomized to intracoronary adenosine or saline. The 2 groups were similar for age, sex, and infarct location. Adenosine administration was feasible and well tolerated. PTCA was successful in all patients and resulted in TIMI 3 flow in all patients given adenosine and in 19 given saline (P<0.05). The no-reflow phenomenon occurred in 1 adenosine patient and in 7 saline patients (P=0.02). Creatine kinase was lower in the adenosine group, and a Q-wave MI developed in 16 adenosine patients and in 23 saline patients (P=0.04). Sixty-four percent of dyssynergic segments improved in the adenosine group and 36% in the saline group (P=0. 001). Function worsened in 2% of dysynergic segments in the adenosine group and in 20% in the saline group (P=0.0001). Adverse cardiac events occurred in 5 patients in the adenosine group and in 13 patients in the saline group (P=0.03).nnnCONCLUSIONSnIntracoronary adenosine administration is feasible and well tolerated in AMI. Adenosine adjunct to primary PTCA ameliorates flow, prevents the no-reflow phenomenon, improves ventricular function, and is associated with a more favorable clinical course.

Prognostic importance of dipyridamole-echocardiography test in coronary artery disease.

We studied the value of dipyridamole-echocardiography test in comparison with clinical, resting electrocardiogram and echocardiogram variables in predicting cardiac events occurring in 539 consecutive patients referred for dipyridamole-echocardiography test from 1984 to 1987. There were 118 cardiac events: 11 cardiac deaths, 12 nonfatal myocardial infarctions, and 95 coronary revascularization (bypass or angioplasty) procedures. A Cox survival analysis identified echocardiographic positivity after dipyridamole administration as the best predictor of cardiac events (relative risk ratio, 2.7). The next most powerful predictor was angina after dipyridamole administration (relative risk ratio, 1.9). Cardiac events occurred in 14 (6%) of 253 patients with normal high-dose dipyridamole echocardiographic test results, in 21 (26%) of 82 patients with high-dose dipyridamole echocardiographic positivity (0.84 mg/kg during 10 minutes), and in 83 (41%) of 204 patients with low-dose dipyridamole echocardiographic positivity (0.56 mg/kg during 4 minutes) (p less than 0.0001). In a subset of 341 patients, exercise electrocardiography stress test and coronary angiography were also available. A Cox survival analysis again identified echocardiographic positivity after dipyridamole as the best predictor of cardiac events (relative risk ratio, 1.9) followed by a pathologic coronary arteriography (relative risk ratio, 1.2). We conclude that the presence and timing of a transient dyssynergy during dipyridamole stress are useful predictors of subsequent cardiac events.

Adenosine-induced renal vasoconstriction in man

OBJECTIVEnThe aim of the study was to evaluate the effects of adenosine on renal blood flow in humans.nnnMETHODSnEleven normotensive patients (mean age 53 +/- 11 years) with normal renal angiograms were enrolled in the study. Arterial blood pressure, one ECG lead and arterial renal blood flow velocity, by intravascular Doppler catheter, were monitored throughout the procedure. Incremental doses (10(-5), 10(-4), 10(-3), 2 x 10(-3), 5 x 10(-3), 10(-2), 10(-1), 1 mg) were selectively injected, at 5-min intervals, in a renal artery.nnnRESULTSnAdenosine administration had no significant effects on blood pressure, heart rate and atrio-ventricular conduction. A progressive reduction in renal blood flow velocity (from 16.36 +/- 1.9 to 3.9 +/- 0.8 cm/s, P < 0.0001) was observed. Following adenosine the decrease of flow velocity was immediate and its duration was proportional to dosage (from 0.5 +/- 0.4 s at 10(-5) mg to 31 +/- 6.5 s at 1 mg). Renal angiography, repeated in four patients during flow velocity decrement, showed no changes in vessel diameter.nnnCONCLUSIONSnExogenous adenosine-induced a marked and transient reduction in renal blood flow in man. This effect suggests that adenosine or its metabolites may be directly implicated in rapid and powerful mechanisms of cardiac output redistribution. Thus endogenous adenosine could have a role in regulating renal blood flow in physiological and pathological situations like strenuous exercise, hemorrhage shock and cardiac failure.

Right ventricular dysfunction is associated with chronic kidney disease and predicts survival in patients with chronic systolic heart failure.

Chronic kidney disease (CKD) and right ventricular (RV) dysfunction are important predictors of prognosis in heart failure (HF). We investigated the relationship between RV dysfunction and CKD in outpatients with chronic systolic HF, an association which remains poorly defined.

Electrocardiographic manifestations and in-hospital prognosis of transient acute myocardial ischemia at rest

From January 1970 to June 1985, transient electrocardiographic changes at rest were documented in 652 patients admitted to our coronary care unit. Patients were stratified according to the type of electrocardiographic alteration at rest: 295 had ST-segment elevation (group 1), 106 T-wave changes (group 2) and 251 ST-segment depression (group 3). Patients in group 3, compared with groups 1 and 2, were more likely to have symptoms of coronary artery disease dating back many years (p less than 0.01 and p less than 0.01, respectively), a previous myocardial infarction (p less than 0.05 and difference not significant), a positive exercise test (p less than 0.01 and p less than 0.01), transient ST-T changes occurring in a higher number of electrocardiographic leads (p less than 0.01 and p less than 0.01), multivessel disease (p less than 0.001 and p less than 0.01) and poor ventricular function (p less than 0.01 and p less than 0.05). Despite these differences, the occurrence of acute myocardial infarction and cardiac death during hospitalization was much more frequent in group 1 compared with groups 2 (p less than 0.02) and 3 (p less than 0.05). However, death occurred in those patients who had poor ventricular function and severe atherosclerosis. A greater susceptibility of group 1 patients to severe vasoconstriction documented by the ergonovine test and by the occurrence of spontaneous spasm seems to account for different in-hospital outcome.

Effects of parasympathetic blockade on ischemic threshold in patients with exercise-induced myocardial ischemia

Abstract In patients with coronary artery disease (CAD), an abnormal coronary vasoconstriction superimposed to organic stenosis may further limit coronary flow reserve. 1 This functional factor can modulate flow availability to the ischemic region and be responsible for the variability of ischemic threshold frequently observed in patients with effort angina pectoris. 2 An imbalance between dilatatory and constrictor stimuli has been postulated in these patients, possibly related to the impairment of the endothelium-mediated regulation of smooth muscle tone. 3 In normal subjects, coronary infusion of acetylcholine produces coronary vasodilation that appears to be mediated by the endothelium-derived relaxing factors, whereas in patients with CAD, it reduces large coronary artery diameter and decreases coronary flow velocity 4 (in animal experiments this latter effect seems to be independent of both α and β blockade, and is promptly reversed by intravenous injection of atropine). 5 A similar phenomenon can be observed during exercise. Compared with normal subjects, patients with CAD have a paradoxical vasoconstriction of large epicardial coronary arteries that can be prevented by treatment with isosorbide dinitrate. 6,7 It can be hypothesized that in normal conditions the parasympathetic system opposes vasoconstriction during exercise, whereas in the absence of endothelium its effect is reversed to coronary vasoconstriction. The aim of this study was to evaluate the effect of atropine, a parasympathetic blocker, compared with that of isosorbide dinitrate, an endothelial independent vasodilating drug, on the ischemic threshold of patients with exercise-induced ischemia.

Association of furosemide dose with clinical status, left ventricular dysfunction, natriuretic peptides, and outcome in clinically stable patients with chronic systolic heart failure.

In chronic heart failure (HF), high daily doses of furosemide have been associated with increased mortality. The authors sought to evaluate the relationships between orally administered furosemide doses, clinical status, left ventricular (LV) dysfunction, N-terminal proBNP (NT-proBNP), and outcome in 400 outpatients with chronic HF and LV ejection fraction (EF) ≤ 45%. Clinical status, NT-proBNP levels, and estimated glomerular filtration rate (eGFR) were evaluated. Median follow-up duration was 32 months. The median values of daily-dose furosemide and of furosemide dose normalized to body surface area were 25 mg (12.5-62.5 mg) and 15 mg/m(2) (13-34 mg/m(2)), respectively. A total of 32% of patients had decompensated HF according to Framingham score and criteria for congestion. In clinically stable patients, a multivariable Cox model, which included clinical and echocardiographic parameters plus NT-proBNP, hemoglobin, and eGFR, showed that normalized furosemide dose (P=.017), anemia (P=.060), age (P=.080), and New York Heart Association class (P=.080) were predictors of all cause-mortality. In patients with decompensated HF, LV end-systolic volume index (P=.018), NT-proBNP (P=.060), and reduced eGFR (P=.070) were independently related to the outcome. Normalized furosemide dose was a major determinant of prognosis in patients with chronic HF but without ongoing signs and symptoms, and this suggests a possible negative interaction of this drug in clinically stable patients.

Usefulness of pirenzepine, an M1 antimuscarinic agent, for effort myocardial ischemia

This study evaluated the effect of pirenzepine, an M1 antimuscarinic agent, on exercise duration and ischemic threshold in patients with angiographically documented coronary artery disease and clear-cut ST depression (greater than 0.2 mV, 0.08 second after the J point) during ergometric stress testing. Twenty-five patients, mean age 56 +/- 8 years, underwent 3 randomized multistage bicycle exercise stress tests after intravenous administration of saline solution (2 ml), isosorbide dinitrate (1 mg) and pirenzepine (2 mg). Isosorbide dinitrate, an endothelium-independent coronary dilating agent, was used as a reference drug. Compared with saline, both pirenzepine and isosorbide dinitrate significantly improved time to ischemia (0.15 mV ST-segment depression) from 6.5 +/- 2 to 7.8 +/- 2 and 8.6 +/- 2 minutes and rate-pressure product at ischemia from 21,498 +/- 4,903 to 24,083 +/- 6,692 and 24,547 +/- 5,390 mm Hg.beats/min, respectively. Compared with saline, pirenzepine did not induce significant changes in blood pressure either at rest or during exercise, whereas it decreased resting heart rate from 71 +/- 9 to 60 +/- 11 beats/min (p less than 0.01) and induced a significant increment of heart rate during ischemia from 117 +/- 18 to 126 +/- 21 beats/min (p less than 0.05). Compared with saline, isosorbide dinitrate reduced systolic blood pressure at rest from 132 +/- 12 to 112 +/- 12 mm Hg, increased heart rate at rest from 71 +/- 10 to 84 +/- 16 beats/min and heart rate at ischemia from 117 +/- 18 to 132 +/- 16 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine causes the release of active renin and angiotensin II in the coronary circulation of patients with essential hypertension

OBJECTIVESnThe aim of the study was to evaluate whether adenosine infusion can induce production of active renin and angiotensin II in human coronary circulation.nnnBACKGROUNDnAdenosine can activate angiotensin production in the forearm vessels of essential hypertensive patients.nnnMETHODSnIn six normotensive subjects and 12 essential hypertensive patients adenosine was infused into the left anterior descending coronary artery (1, 10, 100 and 1,000 microg/min x 5 min each) while active renin (radioimmunometric assay) and angiotensin II (radioimmunoassay after high performance liquid chromatography purification) were measured in venous (great cardiac vein) and coronary arterial blood samples. In five out of 12 hypertensive patients adenosine infusion and plasma samples were repeated during intracoronary angiotensin-converting enzyme inhibitor benazeprilat (25 microg/min) administration. Finally, in adjunctive hypertensive patients, the same procedure was applied during intracoronary sodium nitroprusside (n = 4) or acetylcholine (n = 4).nnnRESULTSnIn hypertensive patients, but not in control subjects, despite a similar increment in coronary blood flow, a significant (p < 0.05) transient increase of venous active renin (from 10.7 +/- 1.4 [95% confidence interval 9.4 to 11.8] to a maximum of 13.8 +/- 2.1 [12.2 to 15.5] with a consequent drop to 10.9 +/- 1.8 [9.7 to 12.1] pg/ml), and angiotensin II (from 14.6 +/- 2.0 [12.7 to 16.5] to a maximum of 20.4 +/- 2.7 [18.7 to 22.2] with a consequent drop to 16.3 +/- 1.8 [13.9 to 18.7] pg/ml) was observed under adenosine infusion, whereas arterial values did not change. Calculated venous-arterial active renin and angiotensin II release showed a strong correlation (r = 0.78 and r = 0.71, respectively; p < 0.001) with circulating active renin. This adenosine-induced venous angiotensin II increase was significantly blunted by benazeprilat. Finally, both sodium nitroprusside and acetylcholine did not affect arterial and venous values of active renin and angiotensin II.nnnCONCLUSIONSnThese data indicate that exogenous adenosine stimulates the release of active renin and angiotensin II in the coronary arteries of essential hypertensive patients, and suggest that this phenomenon is probably due to renin release from tissue stores of renally derived renin.

A computer protocol to evaluate subjects with chest pain in the emergency department: a multicenter study.

Objective Chest pain is a frequent cause of medical admission to the emergency department and the main differential diagnosis is between coronary and non-coronary chest pain. We elaborated a computer protocol for the management of patients with chest pain. Methods The computer protocol was made of three sections according to clinical, electrocardiographic and biochemical data. Each section was coded by a letter indicating the probability of coronary chest pain for each section. The combination of the three letters formed a score string used to assign patients to four subgroups of overall probability of coronary chest pain (low, medium-low, medium-high, and high). Low-probability patients were discharged from the emergency department, whereas high-probability patients were admitted to the coronary care unit. The medium-probability patients underwent further evaluation by means of a stress test and were re-classified as having a final low probability (negative test) or high probability (positive test). Results We evaluated 472 patients (mean age 64 years, range 18–97 years; 47% female). The incidence of coronary events in patients with low, medium-low, medium-high and high overall probability was 1.9, 12.8, 13.5 and 68.0%, respectively (P < 0.05). The positive and negative predictive values of the protocol were 64.7 and 97.1%, respectively. Conclusions Our computer protocol represents a reliable method for the management of patients with chest pain and a non-diagnostic electrocardiogram.