Paolo Marraccini

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.

Coronary hemodynamics and myocardial metabolism in patients with syndrome X: Response to pacing stress

Coronary hemodynamics, myocardial metabolism and left ventricular function at rest and after incremental atrial pacing were evaluated in 12 patients with stress-induced angina and ST segment depression, angiographically normal coronary arteries and no evidence of spasm, generally labeled as syndrome X, and in 10 normal subjects. At baseline study, great cardiac vein flow was comparable in patients and control subjects. During pacing, an equivalent rate-pressure product was reached in the two groups, but the slope of the relation between rate-pressure product and great cardiac vein flow was significantly less steep in patients than in normal subjects (0.0027 vs. 0.0054 ml/mm Hg.beat, p less than 0.001). Nevertheless, the left ventricular ejection fraction was comparable in both groups at rest (66 +/- 6% vs. 71 +/- 7%, p = NS) and during pacing (71 +/- 7% vs. 66 +/- 5%, p = NS). At baseline study, myocardial glucose extraction was more efficient in patients with syndrome X (p less than 0.05), but net myocardial exchange of pyruvate and alanine was, respectively, smaller and greater than in control subjects. Lactate was extracted to a similar extent in the two groups and in no instance was net lactate release observed during pacing or recovery. During pacing and recovery, patients with syndrome X showed net pyruvate release, unlike the control subjects in whom net pyruvate exchange was positive. In addition, patients with syndrome X continued to show net myocardial extraction of alanine during spacing and recovery, whereas normal subjects produced alanine throughout the study. Myocardial carbohydrate oxidation increased significantly during maximal pacing in normal subjects but not in patients, in whom it always remained below (p less than 0.01) the concurrent rate of myocardial uptake of carbohydrate equivalents (glucose, lactate, pyruvate, alanine). Myocardial energy expenditure was significantly lower in patients than in control subjects at maximal rate-pressure product levels (p less than 0.01). The metabolic pattern in patients with syndrome X therefore is not consistent with classic ischemia, although differences in the net exchange of circulating substrates (glucose, pyruvate, alanine) can be demonstrated. Thus, in patients with syndrome X, the symptoms, electrocardiographic signs and impairment in the increase in great cardiac vein flow during pacing coexist with preserved global and regional left ventricular function and myocardial energy efficiency.

Altered coronary vasodilator reserve and metabolism in myocardium subtended by normal arteries in patients with coronary artery disease

OBJECTIVESnThe aim of this study was to investigate coronary vasodilator reserve and metabolism in myocardium subtended by angiographically normal arteries remote from ischemia.nnnBACKGROUNDnAfter infarction, structural and functional changes occur in remote myocardium often subtended by normal arteries. Whether changes occur in regions remote from ischemic but noninfarcted myocardium is unknown.nnnMETHODSnCoronary vasodilator reserve was measured with positron emission tomography in 12 patients with single-vessel disease using intravenous dipyridamole (0.56 mg/kg for 4 min). In another 10 patients, simultaneous arterial/great cardiac vein catheterization was performed during atrial pacing to measure myocardial metabolism in regions subtended by diseased or normal arteries.nnnRESULTSnBasal myocardial blood flow in stenosis-related regions was comparable to that in remote regions but was lower after dipyridamole administration (1.73 +/- 0.91 vs. 2.89 +/- 0.93 ml/min per g, p < 0.01), giving coronary vasodilator reserve values of 1.80 +/- 0.82 and 2.73 +/- 0.89 (p < 0.01). In normal control subjects, basal myocardial blood flow was 0.92 +/- 0.13 and 3.67 +/- 0.94 ml/min per g in the basal state and after dipyridamole (both p < 0.05 vs. values in remote regions), and coronary vasodilator reserve was 4.07 +/- 0.98 (p < 0.01) vs. values in remote regions). During pacing there was net lactate release in diseased regions (-18 +/- 27%, p < 0.05 vs. values in remote regions and control subjects) and extraction in remote regions (38 +/- 17%) and in normal control subjects (26 +/- 11%). Glucose and alanine extraction were increased in diseased (8 +/- 6% and 6 +/- 6%) and remote regions (6 +/- 3% and 4 +/- 3%), compared with values in normal control subjects (2 +/- 3% and -1 +/- 3%, both p < 0.05 vs. diseased and remote regions).nnnCONCLUSIONSnCoronary vasodilator reserve is reduced and glucose and alanine metabolism is abnormal in regions subtended by normal arteries remote from ischemic but noninfarcted myocardium.

Plasma Cholesterol Regulates Soluble Cell Adhesion Molecule Expression in Familial Hypercholesterolemia

BACKGROUNDnHypercholesterolemia is associated with endothelial dysfunction. On the basis of the hypothesis that high plasma cholesterol per se may be a sufficient stimulus to upregulate endothelial adhesiveness and that this phenomenon might be reversible, soluble endothelial leukocyte adhesion molecules (sELAMs) were studied in patients with familial hypercholesterolemia undergoing LDL apheresis.nnnMETHODS AND RESULTSnSelective LDL absorption by dextran sulfate columns was used to treat plasma volumes of 6.5 to 9.2 L; after LDL apheresis, total cholesterol, LDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a) levels were reduced by 74%, 82%, 79%, 56%, and 86%, respectively. Soluble intercellular adhesion molecule-1 (sICAM-1) and sELAM- were measured before, immediately after, and 2 and 6 days after LDL apheresis. Basal sICAM-1 and sELAM-1 values were higher than in healthy control subjects. After LDL apheresis, they decreased (P<.0001 and P<.0004, respectively); their removal by extracorporeal circulation components was excluded. Individual pretreatment and posttreatment values of sICAM-1 and sELAM-1 were positively correlated (P<.0001 and P<.001, respectively) with total cholesterol; their rebound curves showed patterns similar to the total cholesterol rebound curve but not to the triglyceride and lipoprotein(a) curves.nnnCONCLUSIONSnIn the absence of changes in clinical chemical parameters, tumor necrosis factor-alpha, interleukin-6, and acute-phase reactant proteins, these results confirm in a clinical setting the upregulation of endothelial adhesiveness observed in experimental hypercholesterolemia and suggest a direct role for cholesterol in regulating this phenomenon, at least in familial hypercholesterolemia.

Adrenergically mediated coronary vasoconstriction in patients with Syndrome X

SummarySeveral studies have shown that coronary vasodilator reserve is impaired in some patients with chest pain and angiographically normal coronary arteries. In a subgroup of these patients, who additionally show ST depression on the electrocardiogram during exercise and are generally labelled as having Syndrome X, the impairment of coronary flow reserve is associated with metabolic and functional signs consistent with an increased sympathetic drive. The aim of the present investigation was to ascertain whether the impairment of coronary vasodilator reserve in patients with Syndrome X is due to adrenergically mediated vasoconstriction of coronary microcirculation. Myocardial blood flow (MBF), at baseline and following intravenous infusion of dipyridamole (0.56 mg/kg over 4 minutes), was measured by means of13N-ammonia and dynamic positron emission tomography in 10 females (mean age 52±8 years) with a chest pain history, ST-segment depression during exercise, and angiographically normal coronaries. The first MBF study was performed while the patients were off therapy; a repeat MBF study was performed following 1 week of treatment with the alpha-1 blocker doxazosin (2 mg/day). Off therapy MBF was 1.13±0.25 ml/min/g at baseline and increased to 2.35±0.66 ml/min/g following dipyridamole. Coronary vasodilator reserve (dipyridamole/baseline MBF) was 2.18±0.56. During treatment with doxazosin, baseline MBF was not different from the control value (1.25±0.50 ml/min/g), while added dipyridamole significantly increased MBF to 3.52±1.20 ml/min/g (p<0.01 vs. off therapy). Coronary vasodilator reserve was significantly increased (2.91±0.92, p<0.01 vs. control value) by doxazosin. This study indicates that alpha-1 adrenoceptors might play a role in the reduction of coronary reserve in patients with Syndrome X. Further clinical studies are needed to ascertain the efficacy of alpha-1 blockers for the treatment of such 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)