Michele Benz Department of Cardiology, Marshfield Clinic, Marshfield, Wisconsin REPRINT REQUESTS: Shereif H. Rezkalla, MD, Department of Cardiology, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI 54449, Telephone: 715-387-5301, Fax: 715-389-3808, Email: rezkalla.shereif{at}marshfieldclinic.org
BACKGROUND We tested the hypothesis that nifedipine, a calcium channel blocker, could ameliorate the toxic effects of cocaine on the myocardium. METHODS AND RESULTS In an initial protocol, anesthetized dogs were pretreated with nifedipine or saline and then administered cocaine (10 mg/kg, i.v. bolus). Coronary blood flow, heart rate, mean arterial pressure, and the first derivation of left ventricular pressure (dP/dt) were measured at baseline, 2 minutes, and 15 minutes after cocaine administration. Nifedipine pretreatment prevented the early cocaine-induced decrease in coronary blood flow and improved left ventricular dP/dt compared with untreated control animals. After cocaine, ejection fraction fell in the saline group to 37 +/- 3% but increased in the nifedipine group to 59 +/- 4% (p less than 0.05). In a second protocol, vehicle or intravenous nifedipine was administered after an infusion of cocaine (10 mg/kg). In contrast to pretreatment, there was no significant improvement in left ventricular function or coronary blood flow in nifedipine-treated versus control animals. Data from the study also suggested that cocaine acts directly on the myocardium. Within seconds of cocaine bolus administration, coronary blood flow in control animals increased to a peak level 59 +/- 14% higher than before cocaine and left ventricular dP/dt decreased by 23 +/- 5%, providing evidence that cocaine causes direct depression of myocardial function independent of a decrease in myocardial blood flow. CONCLUSIONS We conclude that nifedipine administered as a pretreatment protects against the depression of myocardial function and decrease in coronary blood flow caused by acute cocaine administration. However, when nifedipine is given after cocaine, no improvement is seen. Cocaine has a direct negative inotropic effect on the heart that is independent of a decrease in coronary blood flow.
No-reflow (NR) phenomenon is a well-known problem, often accompanying percutaneous coronary intervention for acute ST elevation myocardial infarction (STEMI). There are little data on effects of pharmacologic therapy on the resolution, outcome, and long-term natural history of NR.Retrospectively assess incidence, management, and prognosis of NR in a tertiary referral hospital.Study included patients with STEMI, treated with percutaneous coronary intervention (PCI). Effect of pharmacologic therapy and long-term outcome were assessed. NR was defined by thrombolysis in myocardial infarction (TIMI) < 3 or myocardial blush grade (MBG) < 3.Of 347 identified subjects, NR occurred in 110 (32%) by TIMI and 198 (57%) by MBG. Higher incidence was identified in men versus women (34% vs. 25% by TIMI, P = 0.08; and 60% vs. 48% by MBG, P = 0.04). Pharmacologic therapy was equally effective in restoring normal flow, increasing TIMI score from 1.62 ± 0.07 to 2.78 ± 0.06 (P < 0.0001) and MBG score from 0.43 ± 0.08 to 2.09 ± 0.11 (P < 0.0001). Twenty-three percent who did not receive pharmacologic therapy developed clinical composite of congestive heart failure, cardiogenic shock, and/or death; only 9% of patients who received pharmacologic therapy developed this composite. Patients with severe NR despite treatment had poorer prognosis. Sixty-five percent of patients who survived and had repeat angiogram about 1.5 years later had spontaneous improvement in coronary flow by MBG.NR is common in STEMI. Treatment with nicardipine, nitroprusside, and verapamil are equally effective in improving flow. If not treated, prognosis is poor.
Rajan Kanth, MD*, Sunitha Ittaman, MD* and Shereif Rezkalla, MD, FACP†⇑ *Department of Internal Medicine, Marshfield Clinic, Marshfield, WI USA †Department of Cardiology, Marshfield Clinic, Marshfield, WI USA Corresponding Author: Shereif Rezkalla, MD, FACP; Department of Cardiology; Marshfield Clinic; 1000 North Oak Avenue; Marshfield, WI 54449; Tel: (715) 387-5845; Fax: (715) 389-5757; Email: rezkalla.shereif{at}marshfieldclinic.org
