Abstract

Nitric oxide eneration by L-Arginine (2 mg/kg/min) infusion during cardiopulmonary bypass (CPB) increases blood flow to all organs and reduces the cytokine induced organ damage by reducing the level of marginating neutrophils (Ns). The N-trapping in the oxygenator (OX), arterial filter (AF), cardiotomy reservoir (CR), and N-margination were quantified with indium 111 labelled autologous neutrophils (INN) in nine groups of 40 Yorkshire pigs (30-35 kg). Cardiopulmonary bypass (180 min or 90 min CPB, 90 min reperfusion) was carried out at 2.5/3.5 L/min and at two temperatures (18ºC and 28ºC). The INN (650-780 microCi) was administered intravenously 15 mins before CPB. All pigs received heparin systematically (activated coagulation time > 400 secs); CPB was instituted with a roller pump, OX (Univox 1.8 m²), AF (0.25 m²), and CR (BCR-3500, Bentley Lab, Irvine, CA). The INN distribution in the device (OX AF, CR) and organs was imaged with a gamma camera and measured with an ion chamber and a gamma counter. The LA infusion decreased N-trapping, estimated as the percent of injected INN (mean ± standard deviation), in OX from control (2.7 ±2.02)% to (0.94 ± 0.29)% and margination in lung from control (48 ± 4)% to minimal levels (23 ± 2)% (p < 0.01). In the CPB reperfusion group, a beneficial effect was observed at LA low dose and toxicity of higher N­margination at 15 mg/kg/min. Neither CPB temperature nor Leumedin affected N­margination significantly. ASAIO Journal 1996;42:M661-M666.

Abstract

The objective of this review is to make physicians aware of new radiomucleotide methods to detect cardiac effect of chemotheraputic drugs. This knowledge is important because of the limitations of the physical examinations and the electrocardiogram for detecting early reversible cardiac damage. Presently left ventricular ejection fraction (LVEF) is routinely used to screen for cardiotoxicity. Since LVEF obtained by radionucleotide angiocardiography is more accurate than the LVEF estimated by echocardiography, serial radionucleotide LVEF is most commonly used to monitor cardiotoxicity. Diastolic measurements of left ventricular function (such a peak filling rate) are now being added to routine LVEF measurements to enhance standard radionucleotide evaluation. This screening test should be done prior to beginning therapy and at appropriate points based on the baseline study, therapy scheme and the patient's clinical status. At some centers, exercise LVEF methods are being used to determine if cardiac reserve is adequate for the patient to tolerate additional chemotherapy when cardiac injury may be present. Previously, endomyocardial biopsy was needed to detect and confirm early antracycline cardiotoxicity. This invasive test may be replacedby a new noninvasive in vivo method using radioactive monoclonal antibodies against cardiac muscle (indium-111-antimyosin). Because cardiac failure has been associated with andrenergic neuron injury, it has been proposed that radioactive methyliodobenzylguanine may detect the adrenergic which may predict future development of congestive heart failure or sudden death months after therapy is discontinued. Advantages and disadvantages of these methods in evaluating cardiotoxicity, and an algoryhtm to optimally monitor antitumor therapy-induced cardiomyopathy are discussed. Oncology 1996;53:461-470.