Mario Marzilli

Global alteration in perfusion response to increasing oxygen consumption in patients with single-vessel coronary artery disease

BACKGROUNDnRecent evidence suggests that, in coronary artery disease (CAD), myocardial blood flow (MBF) regulation is abnormal in regions supplied by apparently normal coronary arteries. However, the relation between this alteration and MBF response to increasing metabolic demand has not been fully elucidated.nnnMETHODS AND RESULTSnMBF was assessed at baseline, during atrial pacing tachycardia, and after dipyridamole (0.56 mg/kg IV over 4 minutes) in 9 normal subjects and in 24 patients with ischemia on effort, no myocardial infarction, and isolated left anterior descending (n = 19) or left circumflex (n = 5) coronary artery stenosis (> or = 50% diameter narrowing). Perfusion of both poststenotic (S) and normally supplied (N) areas was measured off therapy by positron emission tomography and [13N]ammonia. Normal subjects and CAD patients showed similar rate-pressure products at baseline, during pacing, and after dipyridamole. In CAD patients, MBF was lower in S than in N territories at rest (0.68 +/- 0.14 versus 0.74 +/- 0.18 mL.min-1.g-1, respectively, P < .05), during pacing (0.92 +/- 0.29 versus 1.16 +/- 0.40 mL.min-1.g-1, respectively, P < .01), and after dipyridamole (1.18 +/- 0.34 versus 1.77 +/- 0.71 mL.min-1.g-1, respectively, P < .01). However, normal subjects showed significantly higher values of MBF both at rest (0.92 +/- 0.13 mL.min-1.g-1, P < .05 versus both S and N areas), during pacing tachycardia (1.95 +/- 0.64 mL.min-1.g-1, P < .01 versus both S and N areas), and after dipyridamole (3.59 +/- 0.71 mL.min-1.g-1, P < .01 versus both S and N areas). The percent change in flow was strictly correlated with the corresponding change in rate-pressure product in normal subjects (r = .85, P < .01) but not in either S (r = .04, P = NS) or N regions (r = .08, P = NS) of CAD patients.nnnCONCLUSIONSnBesides epicardial stenosis, further factors may affect flow response to increasing metabolic demand and coronary reserve in patients with CAD.

Platelet glycoprotein IIb/IIIa receptor blockade and coronary resistance in unstable angina

OBJECTIVESnWe designed a study to explore the effect of glycoprotein (GP) IIb/IIIa blockade on the atherosclerotic plaque and distal coronary vasculature.nnnBACKGROUNDnPlatelet GP IIb/IIIa blockers have been proven to be beneficial in acute ischemic syndromes. This effect has also been attributed to the prevention of microvascular obstruction, although the underlying mechanisms have not been fully defined.nnnMETHODSnEighteen patients with unstable refractory angina pectoris underwent cardiac catheterization and angioplasty. Trans-stenotic and microvascular resistances to flow were measured at baseline, during hyperventilation, and after intracoronary adenosine. Measurements were repeated early after abciximab administration and after successful percutaneous transluminal coronary angioplasty.nnnRESULTSnHyperventilation induced an ischemic attack in 12 of 18 patients and increased epicardial (12.8 +/- 16.9 vs. 6.1 +/- 6.1 mm Hg/ml per min, p < 0.05) and microvascular (9.9 +/- 7.5 vs. 6.8 +/- 5.8 mm Hg/ml per min, p < 0.05) coronary resistance. Abciximab had no significant effect on epicardial resistance, although it significantly reduced distal coronary resistance under all study conditions, including baseline (4.8 +/- 4.8 mm Hg/ml per min, p < 0.01), hyperventilation (5.1 +/- 5.4 mm Hg/ml per min, p < 0.01), and intracoronary adenosine (2.7 +/- 3.0 vs. 4.3 +/- 4.3 mm Hg/ml per min, p < 0.05). The hyperventilation test became negative in all patients after abciximab administration.nnnCONCLUSIONSnThese observations confirm the immediate beneficial effects of platelet GP IIb/IIIa blockade with abciximab in acute ischemic syndromes and suggest that improvement of microvascular function may play a central role in the mechanism of action of this drug.

Functional and structural correlates of persistent ST elevation after acute myocardial infarction successfully treated by percutaneous coronary intervention

Background: In the thrombolytic era, persistence of ST-segment elevation was considered a marker of left ventricular (LV) aneurysm. ST-segment elevation may still be found persistently raised after successful primary percutaneous coronary intervention (PCI). Echocardiographic correlates of this finding, however, are still poorly known. Methods and results: 82 consecutive patients with first ST-segment elevation myocardial infarction and successful PCI were divided into patients with persistent ST-segment elevation at discharge (sum of ST >4 mm) (nu200a=u200a33) and those without persistent ST-segment elevation (nu200a=u200a49). Conventional and myocardial contrast echocardiography were performed at discharge and at 6 months. At discharge, LV aneurysm was more common in patients with persistent ST elevation (27% vs 8%, p<0.005). Similarly, the wall motion score index was higher (2.5 vs 2.0, p<0.005) and microvascular damage larger (2.3 vs 1.8, p<0.005) in patients with persistent ST-segment elevation. At 6 months’ follow-up, LV volumes were similar in the two groups. Conclusions: After primary PCI, persistent ST-segment elevation is associated with LV aneurysm formation in 30% of cases, it is not associated with significantly larger LV dilatation but with larger microvascular damage and dysfunctioning risk area.

Beneficial effect of post-procedural abciximab in patients undergoing primary coronary angioplasty and presenting with the no-reflow phenomenon

We sought to investigate the effect of post-procedural abciximab on clinical outcome of patients presenting the no-reflow phenomenon after primary angioplasty. We retrospectively selected 38 patients who developed the no-reflow phenomenon after primary angioplasty: 18 received post-procedural abciximab, 20 age- and sex-matched patients who did not receive abciximab were considered as concurrent controls. At 6 months follow-up, the clinical course was uneventful in the abciximab group while the composite end-point of major adverse cardiac events occurred in 8 patients (40%) in the control group (P=0.009). ‘Rescue’ administration of abciximab is an effective option for the treatment of the no-reflow phenomenon determining significant prognostic improvements.

PTCA acutely expands perfused myocardial mass and increases flow homogeneity

In absence of collaterals, coronary stenosis produces a pressure drop in the microcirculation which might compromise capillary pressure and physiological blood—tissue exchanges. The present study tests the hypothesis that a derecruitment of vascular units occurs in the post-stenosis territory to maintain capillary pressure constant and that the restoration of a normal distal coronary pressure by PTCA is able to recruit additional myocardium to perfusion. Nine patients with single left coronary vessel disease, no previous myocardial infarct and normal ventricular function, were studied in a single session, before and after successful PTCA and stenting. Flow entering the stenotic vessel (CBF = ml/min, by Doppler catheter and quantitative angiography), and flow per gram of myocardium downstream the stenosis (MBF = ml/min/g of tissue, by the analysis of radioactive Xenon wash-out curves) were simultaneously measured. Perfused tissue was calculated as CBF/MBF and heterogeneity of flow distribution as the ratio between high and low flow sub-compartments estimated by bi-exponential analysis of Xenon curves. Distal coronary pressure was assessed by pressure wire. Heterogeneity of perfusion was also assessed in the remote region perfused by the angio-graphically normal left coronary branch. Distal coronary pressure during balloon occlusion was 21 ± 10 mmHg. PTCA increased CBF following i.e. adenosine from 19.8 ± 16.1 to 48 ± 27 ml/min, coronary flow reserve from 1.5 ± 0.2 to 2.3 ± 0.8 (p < 0.01) and distal coronary pressure from 68 ± 9 to 99 ± 8 at rest, and from 54 ± 10 to 99 ± 10 mmHg during adenosine. Perfused myocardial volume at rest increased from 27 ± 21 to 39 ± 8 g. A strict correlation was found between the increase in distal coronary pressure and the increase in perfused volume after PTCA (r = 0.79, p < 0.001). Flow homogeneity significantly increased following PTCA to the level of the remote region. In conclusion severe coronary stenosis contracts the amount of normally perfused myocardium likely to preserve capillary pressure and flow reserve in the residual perfused vascular units. PTCA expands perfused volume and decreases flow heterogeneity, according to the increase in distal coronary pressure.

Microcirculatory Function: Coronary Vasculature

Cardiac metabolism is strictly aerobic. The continuous cardiac work implies continuous fuel and oxygen supply and, similar to other organs, an intact coronary circulation. However, in respect to its own vasculature, the heart appears rather unique in the sense that the myocardial contraction represents the primary driving force of the systemic circulation, and the systemic hemodynamics in turn represents the primary driving force of the coronary circulation. Furthermore, the systemic circulatory demands are the primary determinants of the myocardial oxygen consumption and thus of the myocardial perfusion. Because of these mutually dependent characteristics of the systemic and the coronary circulations, coronary hemodynamics is determined not only by the mechanical and biologic properties of the coronary vascular bed, but also by the contractile function of the myocardium. Due to the complexity of the mutual interdependence of the cardiac and systemic circulatory loops, the study of coronary circulation represents a daunting scientific task and a considerable challenge.

Potassium Channel Openers in Therapy, Current Uses, and Perspectives: Cardiac Ischemia and Angina

The myocardial blood flow regulation in coronary artery disease has been a matter of controversy for a long time. In the past, much of the literature focused on the characterization of coronary stenoses which were considered the major determinant of perfusion abnormalities observed in such a disorder. However, it is now well recognized that the hydraulics of epicardial obstruction can not be considered solely responsible for all phenomena which are observed in these patients. In fact, several recent studies demonstrated that atherosclerosis induces more complex changes in vascular physiology, leading to a microvascular dysfunction (and reduced vasodilating capability) even in regions supplied by angiographically normal vessels [1 3]. Although the exact mechanisms of these puzzling findings have not been fully elucidated, several authors suggested that mechanisms regulating coronary blood flow could be much more complex than previously thought and that coronary atherosclerosis might produce profound alterations in vascular smooth muscle and endothelial function in both large epicardial arteries and coronary microvasculature, even in the absence of significant lumen reduction [4 6].