Morphologic characterization of the ice worm Mesenchytraeus solifugus.

Ice worms occupy a unique position in metazoan phylogeny in that they are the only known annelid that completes its life cycle in ice. The mechanism(s) associated with this adaptation are likely to occur at different levels, ranging from modification of their metabolism to changes in morphology. In this study, we examined specimens of Mesenchytraeus solifugus by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in an effort to identify morphologic structures that may aid in its glacial habitation. We report that M. solifugus contains an elongated head pore at the tip of its prostomium, numerous sensory structures, and differentially oriented setae that curve abruptly at their distal end.

Aging and essential hypertension: effect of left ventricular hypertrophy on cardiac function.

This study was designed to analyze the cardiac effects of aging and of hypertension in patients with essential hypertension and with or without left ventricular hypertrophy (LVH). Thirty-one patients <55 years old and 66 patients >64 years old with essential hypertension were divided according to the presence or absence of LVH. Cardiac functional structure was assessed by 2D-guided M-mode echocardiography. The peak filling rate and the duration of rapid filling were obtained by digitizing septal and posterior wall echoes. In the older group only was systolic function significantly impaired in subjects with LVH when compared with subjects without LVH [velocity of circumferential fiber shortening (L/msec): 1.40+/-0.24 v 1.18+/-0.25; fractional fiber shortening (%): 43.06+/-5.02 v 36.26+/-7.1; ejection fraction (%): 81.1+/-5.1 v 73.13+/-9.2; P < .05]. Older patients, even without LVH, showed a longer duration of rapid filling (321.0+/-108.3 msec) and lower peak filling rate (7.01+/-1.86 cm/sec) in comparison with younger persons with or without LVH. In the older subjects the increase in left ventricular mass was associated with a decrease of velocity of circumferential fiber shortening (r = -0.48, P < .01), fractional fiber shortening (r = -0.40, P < .01), and ejection fraction = -0.50, P < .01), whereas there was no correlation in the younger group. The present findings of impaired diastolic filling even in the absence of LVH in the elderly, and the deterioration of systolic function parallel to the increase in LV mass suggest that aging is associated with a decrease in the number of functioning contractile elements per unit of cardiac mass.

Fixed drug combinations in the treatment of hypertension: how to identify the optimal dose.

RATIONALE FOR DRUG COMBINATIONS: The most common reason for combining different drugs is to achieve an additional fall in arterial pressure. It therefore seems reasonable to combine drugs with different mechanisms of actions. NEED FOR CLINICAL TRIALS: However, the effects of combination therapy on the heart and other target organs remains poorly documented. Most of what we know with regard to combination therapy on hypertensive heart disease is based on extrapolation from monotherapy. The fact that two drugs when used separately are beneficial in a disorder does not necessarily imply that their combination is equally or more beneficial in the same disorder. Thus, it will become important to establish efficacy and safety of new drug combinations on hypertensive target organs and on morbidity and mortality by performing carefully designed clinical trials.

Combination therapy and target organ protection in hypertension and diabetes mellitus.

Both essential hypertension and diabetes mellitus affect the same major target organs-the brain, the fundi, the heart, and the kidneys. The common denominator of hypertensive/diabetic target organ disease is the vascular tree. Both hypertension and diabetes are well identified risk factors for atherogenesis. Coronary artery disease is much more common in diabetic hypertensive patients than in patients suffering from hypertension or diabetes alone. Typical for the diabetic hypertensive heart are extensive degenerative changes and a greater degree of hypertrophy compared with the nondiabetic hypertensive heart. The combined presence of hypertension and diabetes concomitantly affects glomerular filtration rate and renal blood flow, thereby greatly accelerating a decrease in renal function. Hypertension accelerates the development of diabetic retinopathy; hypertensive/diabetic cerebral disease leads to vascular dementia, transient ischemic attacks, and strokes. A decrease in the hemodynamic and glycemic burden is the primary goal in the management of the hypertensive diabetic patients. Both diuretics and beta-blockers have been reported to adversely affect the overall risk factor profile in the diabetic patient. In contrast, the postsynaptic alpha-blockers, the calcium antagonists, and the angiotensin-converting enzyme inhibitors have been reported to be either neutral or beneficial with regard to the overall metabolic risk factor profile. The combination of a heart rate lowering calcium antagonist, particularly verapamil, with an ACE inhibitor offers some potential to either prevent or reverse target organ disease associated with hypertension and diabetes.

Cardiac effects of combination therapy.

Control of hypertension and treatment of concomitant pathophysiologic conditions require use of multiple drugs. Unfortunately, most studies regarding hypertensive disease have focused on monotherapy. Thus, our knowledge of combination therapy in the treatment of hypertension is, to a great extent, extrapolation from monotherapy. Angiotensin converting enzyme (ACE) inhibitors in combination with calcium antagonists should be particularly efficacious in reducing left ventricular hypertrophy (LVH). Drug classes that either stimulate the renin-angiotensin system or the sympathetic nervous system are less likely to reduce LVH and should be avoided. In hypertensive patients with congestive heart failure, amlodipine should be added to triple therapy with an ACE inhibitor, whereas in the postmyocardial ischemia patient, verapamil may exert some additional beneficial effects with regard to reinfarction rates. Given that two drugs when used separately are beneficial in a disorder does not necessarily mean that their combination is equally or even more beneficial. Thus, combination therapy should primarily be used for lowering arterial pressure and only secondarily to possibly improve concomitant pathophysiologic conditions associated with hypertensive heart disease.

Cardiac effects of calcium antagonists in systemic hypertension.

The calcium antagonists are a class of heterogeneous drugs, with a wide spectrum of direct and indirect cardiac effects that vary a great deal from one drug to another and depend upon formulation and duration of action. Calcium antagonists act by decreasing total peripheral resistance to lower arterial pressure. As a consequence, reflex tachycardia, increased cardiac output, and increased plasma catecholamine and plasma renin activity are commonly seen, particularly with the initial dose and with short-acting dihydropyridines. The abrupt vasodilation can paradoxically elicit angina and even acute myocardial infarction. These hemodynamic and neuroendocrine changes are less pronounced with the long-acting formulations. Most calcium antagonists diminish automaticity of the sinus node, slow conduction in the atrioventricular node, and have little, if any, effect on the automaticity of the myocytes. The dihydropyridines generally have less effect on automaticity and cardiac conduction than nondihydropyridines. The negative inotropic effect is most profound with nondihydropyridines and is greatly reduced or absent with newer dihydropyridines, such as isradipine, felodipine, amlodipine, and nisoldipine. Long-acting calcium antagonists generally improve myocardial oxygenation by unloading the heart, increasing coronary blood flow, and reducing myocardial oxygen consumption. Thus, calcium antagonists have a variety of beneficial effects in patients with hypertensive heart disease: they reduce left ventricular hypertrophy and its sequelae, such as ventricular dysrhythmias, impaired filling and contractility, and myocardial ischemia. Ongoing studies should provide a more conclusive answer regarding the efficacy and safety of calcium antagonists.

Systemic and regional hemodynamic effects of gallopamil in patients with essential hypertension.

Systemic and regional hemodynamics were assessed in 10 patients with uncomplicated mild to moderate essential hypertension before and during gallopamil therapy. Cardiac output was measured in triplicate with indocyanine dye. Plasma volume and renal blood flow were measured radioisotopically. Immediately following the initial dose of a slow-release (SR) formulation of gallopamil, a significant fall in arterial pressure associated with a decreased total peripheral resistance and a reflex increase in heart rate and cardiac output were seen. Then, after 8-12 weeks of treatment, arterial pressure and total peripheral resistance remained reduced, but heart rate and cardiac output returned to pretreatment levels. Gallopamil also produced significant reductions in renal and splanchnic vascular resistance. Plasma volume and total blood volume did not change. Thus, gallopamil reduced arterial pressure and vascular resistances without fluid retention or prolonged reflexive changes.

Cardiovascular effects of a trandolapril/verapamil combination in patients with mild to moderate essential hypertension.

The cardiovascular effects of a combination of trandolapril and verapamil were evaluated in 14 patients with mild to moderate essential hypertension. This combination therapy decreased arterial pressure mainly through a decrease in total peripheral resistance without causing an increase in heart rate or cardiac output: left ventricular mass was significantly reduced, cardiac systolic function improved, and plasma volume and renal blood flow remained unchanged.

Effects of combination therapy on the heart.

The presence of left ventricular hypertrophy (LVH) usually indicates that hypertension is moderately severe and that combination therapy will be required to control blood pressure (BP). Unfortunately, most studies on the reduction of LVH have been done with monotherapy. Our knowledge of combination therapy in the treatment of hypertensive heart disease is to a great extent extrapolation from monotherapy. Angiotensin-converting enzyme (ACE) inhibitors in combination with calcium antagonists ought to be particularly efficacious in reducing LVH. Drug classes that either stimulate the renin angiotensin system or the sympathetic nervous system are less likely to reduce LVH and should be avoided. In hypertensive patients with congestive heart failure, amlodipine should be added to triple therapy with an ACE inhibitor, whereas in the post myocardial ischemia patient, verapamil may exert some additional beneficial effects with regard to reinfarction rates. Of note, given that two drugs when used separately are beneficial in a disorder does not necessarily mean that their combination is equally or even more beneficial. Thus, combination therapy should primarily be used for lowering arterial pressure and only secondarily to possibly improve concomitant pathophysiologic conditions associated with hypertensive heart disease.