Ornella Rimoldi

Cardiovascular effects of methamphetamine in Parkinson's disease patients

Cardiovascular responses after intravenous methamphetamine were assessed in 11 Parkinsons disease (PD) patients. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and electrocardiogram (ECG) were monitored for 103 minutes. After methamphetamine administration, SBP and DBP increased significantly in both PD and normal controls whereas placebo had no effect. In PD patients, however, the duration of SBP and DBP responses to methamphetamine and the maximum increase from baseline was attenuated compared with the controls. A significant correlation was found between individual BP responsiveness and the Unified Parkinsons Disease Rating Scale (UPDRS) motor score. These findings suggest that in PD there is impairment of catecholamine release from peripheral sympathetic presynaptic terminals, which correlates with motor impairment.

Pathophysiology and diagnosis of hibernating myocardium in patients with post-ischemic heart failure : the contribution of PET

Identification and treatment of hibernating myocardium (HM) lead to improvement in LV function and prognosis in patients with post-ischemic heart failure. Different techniques are used to diagnose HM: echocardiography, MRI, SPECT and PET and, in patients with moderate LV impairment, their predictive values are similar. There are few data on patients with severe LV dysfunction and heart failure in whom the greatest benefits are apparent after revascularization. Quantification of FDG uptake with PET during hyperinsulinemic euglycemic clamp is accurate in these patients with the greatest mortality risk in whom other techniques may give high false negative rates.The debate on whether resting myocardial blood flow to HM is reduced or not has stimulated new research on heart failure in patients with coronary artery disease. PET with H215O or13NH3 has been used for the absolute quantification of regional blood flow in human HM. When HM is properly identified, resting blood flow is not different from that in healthy volunteers although a reduction of ∼20% can be demonstrated in a minority of cases. PET studies have shown the main feature of HM is a severe impairment of coronary vasodilator reserve that improves after revascularization in parallel with LV function. Thus, the pathophysiology of HM is more complex than initially postulated. The recent evidence that repetitive ischemia in patients can be cumulative and lead to more severe and prolonged stunning, lends further support to the hypothesis that, at least initially, stunning and HM are two facets of the same coin.

The Role of Positron Emission Tomography

The link between myocardial ischemia and obstructive atherosclerosis of the epicardial coronary arteries is well established, and coronary angiography has demonstrated a relationship between the severity and extent of coronary artery disease (CAD) and survival. In the past 20 years technological advances in positron emission tomography (PET) have enabled the noninvasive measurement of absolute (ml/min/g) myocardial blood flow (MBF) and flow reserve. In the absence of detectable CAD, a reduced maximum MBF and CFR can be ascribed to coronary microvascular dysfunction.

Myocardial ischemia & viability

The increasing use of thrombolytic therapy and primary percutaneous coronary interventions in association with optimized anti-thrombotic therapy has contributed to significantly reducing short-term mortality and morbidity in patients with acute coronary syndromes. The change of the epidemiology of myocardial infarction over the past 2 decades is due to the increase in NSTEMI infarctions counterbalanced by a substantial reduction in ST-segment elevation [1]. Nevertheless, no further improvement in long term survival could be observed, probably due to the greater number of patients with residual left ventricular (LV) dysfunction undergoing progressive LV remodeling and congestive heart failure (CHF). A problem compounded by the rising age of the population and the higher prevalence of co-morbidities such as diabetes mellitus and hypertension which confer an increased risk of coronary artery disease (CAD) and CHF. Patients with CAD represent by far the most numerous cohort amongst those with CHF and their treatment remains a partial success [2].

The Coronary Microcirculation and Myocardial Ischemia

In normal human beings baseline myocardial energy expenditure in the anterior wall of the left ventricle, calculated from arterial and great cardiac vein substrate concentration and blood flow, amounts to 34±5 cal/min, which means roughly 2–3 times as much for the whole left ventricle. In the post- absorptive state energy is derived almost entirely from free fatty acids and 301±53 pmol/min of oxygen are required for their oxidation. If heart rate is doubled by atrial pacing from 80 to 160 beats per minute, energy expenditure increases to 64±7 cal/min and oxygen consumption to 593±71 pmol/min. These changes occur despite a fall in transmyocardial oxygen extraction from 71+3 to 64+3% from baseline to pacing tachycardia. The additional oxygen required can therefore be delivered only through an increase in myocardial blood flow which, in this particular case, is more than doubled1.