Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1999-06-04
2000-11-28
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
A61K 31135
Patent
active
061536547
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention concerns a method for improving the outcome of cardiac surgery in patients who undergo cardiopulmonary bypass on a heart lung machine. More specifically, this invention concerns administration of therapeutic agents to improve objective measures of surgical outcome.
BACKGROUND OF THE INVENTION
Coronary artery bypass graft (CABG) surgery is an increasingly common treatment for ischemic heart disease. In this procedure, a reversed segment of the patient's own saphenous vein or internal mammary artery is anastomosed between the ascending aorta and one or more stenotic coronary arteries. The anastomosis allows blood from the aorta to bypass atherosclerotic occlusions in the coronary vessels that are producing myocardial ischemia and symptoms of angina.
CABG surgery is performed with the assistance of a heart-lung machine, which temporarily performs the gas exchange function of the lungs and the blood pumping function of the heart. Use of this machine in cardiac surgery is referred to as cardiopulmonary bypass (CPB), and it allows the heart to be arrested (using cardioplegia) during the surgery while blood is shunted through a venoarterial bypass circuit. This circuit performs extracorporeal oxygenation of the blood, and returns it to the arterial tree, bypassing the heart and the pulmonary circulation. CPB allows the surgeon to operate in a bloodless field on a motionless heart.
Although CABG surgery (and use of CPB) have substantially improved the therapeutic outcome of patients with advanced myocardial ischemia, this surgery still has several undesired consequences. Technetium pyrophosphate studies have shown that perioperative myocardial infarctions occur in 21-31% of all CABG patients. Even more highly sensitive Indium-111 monoclonal antibody scintigraphy has shown that perioperative myocardial damage was present in 82% of uncomplicated CABG surgeries. Such damage is particularly troublesome in patients who have unstable angina and already compromised myocardium, because this perioperative damage can further impair heart function.
Induction of anesthesia is complicated in patients with coronary artery disease (CAD) because inhalational anesthetic agents can induce hemodynamic swings in already myocardially compromised patients. Perioperative arrhythmias can complicate the postoperative recoveries of between 20% and 30% of patients following CABG surgery. Some of these events may be due to endogenous catecholamine release caused by the stress of surgery. Although beta adrenergic antagonists (such as propranolol) have long been known to block catecholamine mediated adrenergic responses, use of beta adrenergic antagonists in heart patients has long been viewed with caution. Traditional medical teaching has been that beta adrenergic antagonists are negative inotropes, which decrease the contractility of the heart muscle. Beta adrenergic antagonists (also known as beta blockers) have therefore been used cautiously in patients who have myocardial compromise.
High doses of beta adrenergic antagonists have been assiduously avoided intraoperatively in CABG patients prior to CPB, because conventional medical teaching has been that beta blockers will cause undesirable myocardial depression. Such myocardial depression has been considered particularly unwise in CPB because it has been thought to increase the difficulty of weaning a patient from CPB. Beta blockers have been thought to interfere with the pharmaceutical action of inotropic drugs, such as dopamine or epinephrine, that may be needed to wean a patient from the heart lung machine.
Yet another problem encountered after CABG surgery is neurological or neuropsychiatric compromise. About 2-6% of cardiac surgery patients sustain unequivocal neurologic injury (such as a frank stroke) in the perioperative period. As many as 30-60% of adult cardiac surgery patients experience more subtle neurologic abnormalities or neuropsychiatric changes. About 20-30% of patients still exhibit measurable decrements in neuropsychiatric perfor
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