Sudden unexpected death.

Sudden unexpected death is a major public health problem. Many cases could be prevented if they were anticipated through means of a better awareness among the medical community, new therapies based on early genetic screening, or corrected by countershock.

Studies comparing low molecular weight heparin with heparin for the treatment of thromboembolism: a literature review.

The use of heparin for the prophylaxis and treatment of venous and arterial thrombosis had been the standard of care for clinicians until 1982. At that time the introduction of depolymerized heparin for the prophylaxis of deep vein thrombosis in surgical patients was introduced. A number of such products, low molecular weight heparins (LMWH) were patented and introduced as new drugs during the ensuing of 20 years. Each LMWH had to be given a clinical trial against standard heparin for the several thromboembolic disorders for which heparin was the standard of care. By definition LMWH had to have unequal factor Xa and IIa inhibitor potency, expressed as a Xa-IIa ratio of greater than 1. They also had a molecular weight reduction to about one third that of heparin. A major advantage of LMWH over heparin was the subcutaneous route of injection for treatment of thrombotic disorders in contrast to the intravenous route for heparin. They had greater bioavailability than heparin by the subcutaneous route, a longer half-life and better predictability of dose response. It was found that routine laboratory monitoring was unnecessary. When given a trial against heparin, LMWH was equally safe and effective for most venous and arterial disorders. A new synthetic version of (pentasaccharide) both heparin and LMWH has been at least if not more effective than one LMWH (enoxaparin).

Cardiac dysrhythmias in the conscious dog after surgically induced autonomic imbalance.

The ventrolateral cardiac nerve in the dog is a primary branch of the left sympathetics and represents a direct neural link between the central nervous system and the heart. Its electric excitation elicits characteristic shifts in pacemaker and tachydysrhythmias related to its explicit innervation of the inferior atrial, atrioventricular (A-V) junctional and ventricular tissues. Total denervation of the canine heart, sparing the ventrolateral cardiac nerve, produced a long-term model in which only these portions of the heart retained their sympathetic innervation. The trained unanesthetized model dog was subjected to severe exercise in order to determine the effects of elevated levels of sympathetic tone upon these important regions of the conduction system. Reproducible tachydysrhythmias were elicited in all six animals completing the regimen of periodic testing over a period of 136 to 378 days after operation. The abnormal rhythms consisted of shifting cardiac pacemakers and supraventricular A-V junctional and ventricular tachycardias with frequent premature systoles. Comparable abnormalities were not observed in a similarly tested sham-operated animal or in dogs with a totally denervated heart. The exercise-induced dysrhythmias gradually disappeared with time, presumably in relation to autonomic reinnervation of the heart. The characteristic patterns of ventrolateral cardiac nerve and upon its presumed influence upon Purkinje fiber and A-V nodal automaticity and temporal dispersion of refractoriness in myocardial tissues.

Hierarchy of supraventricular pacemakers.

Definitive subsidiary atrial pacemakers (SAPs) exist within the crista terminalis and in the atrial free wall tissue at the junction of the inferior vena cava and the inferior right atrium. These pacemakers are capable of maintaining cardiac rhythm at a rate intermediate between that of the sinoatrial (SA) nodal and atrioventricular (AV) junctional pacemakers upon default of the normal SA nodal cells. The conventional concept of a single (junctional) escape mechanism needs to be updated by recognition of these SAP sites, which are under comprehensive autonomic regulation. A great variety of clinically important cardiac syndromes require understanding of the SAPs, not only for diagnostic significance but also for therapeutic consideration. SAPs differ from the SA pacemakers in that they possess intrinsically slower spontaneous rates and are less stable. There is early competition among them for instantaneous dominance. They are more responsive to both sympathetic and parasympathetic control, and they are initially more susceptible to underdrive stimulation by another pacemaker (whether artificial or natural) than are pacemakers with the SA node.

Safety of warfarin anticoagulation in patients with heparin-induced thrombocytopenia.

OBJECTIVES: Venous limb gangrene has been reported to occur after high warfarin doses in heparin-induced thrombocytopenia (HIT), and this observation has been used to exclude warfarin management in this condition. The outcome of patients receiving modest doses of warfarin was studied. DESIGN: Retrospective study of 114 consecutive HIT patients who received diagnoses by platelet aggregometry; 51 of the 114 patients received warfarin. SETTING: Tertiary-care medical center. RESULTS: Thirty-five patients received warfarin for non-HIT indications, and 16 received warfarin for heparin-associated thrombosis. Warfarin was given to 23 patients (47%) 2.4 +/- 0.4 days prior to the onset of HIT, in 19 while receiving IV heparin for an overlap of 2.7 +/- 0.4 days. Twenty-eight patients (53%) received warfarin 2.8 +/- 1.0 days after the diagnosis of HIT. Patients received 11 +/- 1 doses of warfarin over 16 +/- 2 days, with a mean daily dose of 3.5 +/- 0.5 and a maximum dose of 9 +/- 0.5 mg. Prothrombin time at discharge was 17.3 +/- 0.4 s with a maximum of 22.8 +/- 0.8. The final international normalized ratio was 2.9 +/- 0. 3, and the maximum was 7.5 +/- 1.4. The minimum therapeutic range was reached in 59% of determinations. When compared to the 63 patients who did not receive warfarin, warfarin patients received more IV heparin (86% vs 41%; p < 0.001), open heart surgery (78% vs 43%; p < 0.001), and had a lower mortality (8% vs 43%; p < 0.001), but had no differences in thrombosis. CONCLUSIONS: Modest doses of warfarin were not associated with a worse outcome in patients with HIT.

Surgical interruption of postganglionic innervation of the sinoatrial nodal region.

Recent experiments have revealed synapses that selectively mediate right and left vagal regulation of sinoatrial function in the fat pad overlying and surrounding the right pulmonary vein complex. However, precise vagal postganglionic pathways to the sinoatrial region have remained obscure. Such pathways, including critically important neural inputs to sinoatrial and atrioventricular nodal regions, may be vulnerable to surgical approaches to atrial or intracardiac repair. The present experiments seek to delineate specific autonomic pathways to the sinoatrial region of the canine heart. The distal ends of the cut right and left cervical vagi and the right and left ansae subclaviae were electrically stimulated (10 to 20 Hz, 1 msec, 2 to 3 V) before and after surgical incisions were placed. Cut No. 1 was made longitudinally along the ventral caval surface from the pericardial reflection caudally to the pulmonary vein fat pad, cut No. 2 was made from the caudal end of cut No. 1 transversely across the sulcus terminalis to a point midway across the anterior (ventral) surface of the right atrium. Each incision was closed with 4-0 silk, with care being taken to avoid injury to either the sinoatrial nodal or the pulmonary fat pad regions. In four of seven animals, these two incisions totally interrupted vagal input to the sinoatrial node, whereas in the remaining three dogs a residual inhibitory influence remained. These residual fibers were surgically ablated by excision of globular fat pads situated on the rostrodorsal surfaces of the right superior pulmonary vein, suggesting a dorsorostral route into the interatrial septum and thence to the sinoatrial node. There was little or no interruption of either right or left vagal input to the atrioventricular nodal region; sympathetic supplies to both sinoatrial nodal and atrioventricular nodal regions remained essentially intact after the two incisions. Thus the major parasympathetic postganglionic projections to the sinoatrial node in the dog heart are by way of the free wall of the right atrium and are vulnerable to surgical interventions in this portion of the heart.

Topography of cardiac ganglia in the adult human heart.

Published descriptions of the topography of cardiac ganglia in the human heart are limited and present conflicting results. This study was carried out to determine the distribution of cardiac ganglia in adult human hearts and to address these conflicts. Hearts obtained from autopsies and heart transplant procedures were sectioned, stained, and examined. Results indicate that the largest populations of cardiac ganglia are near the sinoatrial and atrioventricular nodes. Smaller collections of ganglia exist on the superior left atrial surface, the interatrial septum, and the atrial appendage-atrial junctions. Ganglia also exist at the base of the great vessels and the base of the ventricles. The right atrial free wall, atrial appendages, trunk of the great vessels, and most of the ventricular myocardium are devoid of cardiac ganglia. These findings suggest modifications to surgical procedures involving incisions through regions concentrated with ganglia to minimize arrhythmias and related complications. Repairs of septal defects, valvular procedures, and congenital reconstructions, such as the Senning and Fontan operations, involve incisions through areas densely populated with cardiac ganglia. The current standard procedure for orthotopic heart transplantation severs cardiac ganglia and their projections to nodal and muscular tissue. One modification of the current heart transplantation procedure, involving bicaval anastomosis, preserves atrial anatomy and the cardiac ganglia. Preservation of cardiac ganglia within the donor heart may provide additional neuronal substrate for intracardiac processing and targets for regenerating nerve fibers to the donor heart.

Anticoagulant therapy of pregnant patients with prosthetic heart valves: rationale for a clinical trial of low molecular weight heparin.

The management of anticoagulant therapy for the prevention of thromboembolism from prosthetic heart valves in the pregnant patient is far from ideal and deserves more clinical research. Warfarin therapy given alone throughout pregnancy poses high risks to the fetus because it crosses the placental barrier. Heparin alone throughout pregnancy poses high risks to the mother, which might be lessened somewhat by more intensive therapeutic regimens and careful monitoring of the heparin level or anticoagulated state of the blood. Because of the major risk of embryopathy in the fetus during the first trimester and latter half of the third trimester, heparin therapy during those times has been recommended. In the opinion of some experts, high-risk cases may benefit from low-dose aspirin in addition to anticoagulant therapy. The fact that warfarin is contraindicated during pregnancy (according to the pharmaceutical company that markets it) poses some problems for the physician who prescribes it. For the above reason, alternative drugs are worthy of consideration and should be given clinical trials. Low molecular weight heparin has the potential for greatly reducing drug-related risk for the fetus while providing greater safety for the mother.

Acute venous thrombosis. Therapeutic choices for superficial and deep veins.

Superficial thrombophlebitis is common in varicose veins or veins that have undergone trauma from catheters or intravenous medications. Pain and tenderness, warmth, and erythema are diagnostic features. A compression bandage and nonsteroidal antiinflammatory agent are often all that is required for treatment. Deep vein thrombosis occurs in veins beneath the deep fascia of the leg or in the pelvis or abdomen. It is often asymptomatic but must be treated to prevent pulmonary embolization and postthrombotic syndrome. Standard therapy is administration of heparin sodium for 5 days, followed by tapering and discontinuation. Warfarin sodium (Coumadin, Panwarfin, Sofarin) is sometimes given simultaneously. Longer courses of anti-coagulation therapy are necessary in patients with an ongoing risk of recurrence.

Signal-averaged electrocardiography. Promising tool for predicting sudden cardiac death.

Signal-averaged electrocardiography has shown great promise as an adjunct in identifying patients at risk for sudden cardiac death. Clearly, much research remains to be done. Methods and criteria must be standardized so studies can be compared and the most effective ways in which to use this technology can be determined.

The debut of geriatric medicine.

The transition from mystical to scientific medicine for the aging patient is in part due to the observations of Christoph Wilhelm Hufeland. Though centuries old, his observations ring true even for today's comprehensive therapy.

The dual challenge of electric injury.

(1) Life, lesions and litigation after electrical injury demand skillful immediate medical care. (2) Conscientious application of basic principles provides simple effective management.

Escalating health care costs: costs of litigation.

Although controlling the risks and costs of litigation is difficult, that goal is worth pursuing. Trumped-up malpractice claims, direct litigation costs, and defensive medicine contribute to the accelerating costs of U.S. health care but are not their driving force.

Acute myocardial infarction 2000 treatment.

As the leading cause of death and a major cause of suffering and medical expense, modern management of acute myocardial infarction is essential. Although diagnosis and treatment have become complicated, recent improvements can be initiated by primary care physicians.

Acute myocardial infarction 2000 recognition.

Acute myocardial infarction occurs in two forms: unheralded attacks and those preceded by unstable angina. As the leading cause of death in the US, accounting for over 95 billion dollar annual cost, acute myocardial infarction requires up-to-date recognition and management.

Thromboembolic disease during pregnancy: problems with anticoagulant therapy.

Thromboembolic complications of pregnancy and the puerperium deserve renewed attention not only because they are the most frequent nonobstetrical complications encountered in these circumstances, but also because of current litigious attitudes, the greater survival of women with prosthetic heart valves, and the inadequacy of current treatment regimens that put the physician, as well as the patient, in special peril. New techniques are available to the clinical laboratory for studying the coagulation and hypocoagulant proteins, coagulation inhibitors, and the fibrinolytic system. They provide fresh insight into this perplexing medical problem. Attention to the details of current investigations, efforts to control the risk factors, and the perspicacious use and suitable monitoring of pharmacological agents can be expected to reduce the risks for both the pregnant patient and her attending physicians.

Anticoagulant therapy of thromboembolic disease during pregnancy.

There is growing interest in low molecular weight heparin for the management of thromboembolic disease in pregnancy. Greater understanding of the risk of thromboembolic disease versus the risk of various management practices is urgently needed to reduce maternal mortality and embryopathy in the fetus.