Role of arterial baroreceptors in mediating cardiovascular response to exercise.

The role played by the major arterial baroreceptor reflexes in the cardiovascular response to exercise was examined by comparing the responses of untethered conscious dogs instrumented for the measurement of aortic pressure and cardiac output with those of dogs with total arterial barorecptor denervation (TABD). Moderately severe levels of exercise (12 mph) in intact dogs increased cardiac output from 111 +/- 17 ml/kg per min, increased heart rate from 101 +/- 5 to 265 +/- 8 beats/min, and reduced total peripheral resistance from 0.039 +/- 0.003 to 0.015 +/- 0.002 mmHg/ml per min. Dogs with TABD responded in a very similar fashion; exercise increased cardiac output from 119 +/- 8 to 356 /+- 23 ml/kg per min, increased heart rate from 122 +/- 7 to 256 +/- 5 beats/min, and decreased total peripheral resistance from 0.042 +/- 0.005 to +/- 0.015 +/- 0.001 mmHg/ml per min. The reflex heart rate responses to intravenous bolus doses of methoxamine were also examined in intact animals, both at rest and during exercise. Methoxamine caused striking bradycardia at rest, but little bradycardia during exercise. These results suggest that the arterial baroreceptor reflex is normally turned off during severe exercise and thus does not modify significantly the cardiovascular response to exercise.     

The use of beta-blockers after myocardial infarction

Several beta-blockers have now been shown to be effective in reducing total mortality during the extended recovery period after myocardial infarction. The rate of occurrence of reinfarction and sudden death is also reduced. While the exact mechanisms of this beneficial effect are unknown, it appears to result from a "class" effect, ie, secondary to beta-blockade, since neither cardioselectivity, intrinsic sympathomimetic activity, nor membrane-stabilizing activity appears to be requisite. The reduction in mortality is seen in all age groups, for all types of infarction, and in all risk groups. On the basis of presently available evidence, in patients without contraindication to beta-blockade, prophylactic treatment with beta-blockers should be initiated between one and four weeks after myocardial infarction. The dosage should be sufficient to blunt the heart rate response to exercise, and therapy should be continued for at least two years. The positive results of several well-designed and conducted studies have proved that the concept of secondary prevention is a valid one and should help to save thousands of lives in the coming decade. It is expected that ongoing investigations will determine the efficacy and safety of earlier institution of beta-blockade, including IV administration in the peri-infarction period. The effectiveness of secondary prevention with other agents, including calcium channel blockers, antiplatelet agents, anticoagulants, lipid-lowering drugs, antiarrhythmics, prostacyclin analogues, and thromboxane synthetase inhibitors, should be investigated further. Additional information is needed on the mechanisms by which beta-blockers reduce mortality, sudden death, and reinfarction, on whether specific beta-blockers and/or specific types of beta-blockers have the greatest benefit, and, as a result of further analysis from some of the studies already published, the effect of beta-blockade after myocardial infarction on angina, rhythm disturbances, lipid profile abnormalities, and the quality of life.     

Patency of the infarct-related coronary artery and ventricular geometry.

The pathogenesis of acute myocardial infarction (AMI) involves a sudden thrombotic occlusion of a coronary artery. Spontaneous or pharmacologic thrombolysis may lead to myocardial salvage if patency is achieved within a narrow time window. However, patients in whom thrombolysis occurs late seem to demonstrate improved left ventricular (LV) function and prognosis, which may be independent of myocardial salvage. Preservation of normal LV geometry by reducing expansion of the infarcted segment is a likely mechanism for this benefit. Infarct expansion is most pronounced in patients with anterior wall AMI who have a persistently occluded infarct-related vessel. This process of expansion leads to early increases in LV volume and distortions of LV contour (abnormal LV geometry). Patients whose infarct segment is largest, patients who have manifested infarct expansion, and patients with a persistently occluded infarct-related artery are at highest risk for progressive LV dilation. Experimental data support the concept that reperfusion of occluded vessels that occurs too late for myocardial salvage will preserve LV geometry by limiting infarct expansion. Prospective clinical trials should address whether there is a late, "second time window" during which infarct expansion and distortions of LV geometry may be reduced by (1) therapy with thrombolytic agents applied late after infarction, (2) late mechanical reperfusion with percutaneous transluminal coronary angioplasty (PTCA) or related methods, and (3) load-reducing agents to decrease remodeling, such as angiotensin-converting enzyme inhibitors or nitroglycerin.     

The ten advances that have defined modern cardiology

Modern cardiology was born early in the twentieth century. Here I list and review what I believe to be the ten most important advances in the twentieth century in this field. They are as follows: electrocardiography, cholesterol-induced atherosclerosis, cardiac catheterization, cardiovascular surgery, coronary angiography and percutaneous coronary angioplasty, the coronary care unit, the development of new cardiovascular drugs, preventive cardiology, cardiac imaging, and implanted cardiac pacemakers/defibrillators.     

Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic Trial

OBJECTIVES: The goal of this study was to evaluate combinations of eptifibatide with reduced-dose tenecteplase (TNK) in ST-elevation myocardial infarction (STEMI). BACKGROUND: Glycoprotein IIb/IIIa inhibitors enhance thrombolysis. The role of combination therapy in clinical practice remains to be established. METHODS: Patients (n = 438) with STEMI <6 h were enrolled. In dose-finding, 189 patients were randomized to different combinations of double-bolus eptifibatide and reduced-dose TNK. In dose-confirmation, 249 patients were randomized 1:1 to eptifibatide 180 microg/kg bolus, 2 microg/kg/min infusion, and 180 microg/kg bolus 10 min later (180/2/180) plus half-dose TNK (0.27 mg/kg) or standard-dose (0.53 mg/kg) TNK monotherapy. All patients received aspirin and unfractionated heparin (60 U/kg bolus; infusion 7 U/kg/h [combination], 12 U/kg/h [monotherapy]). The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 epicardial flow at 60 min. RESULTS: In dose-finding, TIMI grade 3 flow rates were similar across groups (64% to 68%). Arterial patency was highest for eptifibatide 180/2/180 plus half-dose TNK (96%, p = 0.02 vs. eptifibatide 180/2/90 plus half-dose TNK). In dose-confirmation, this combination, compared with TNK monotherapy, tended to achieve more TIMI 3 flow (59% vs. 49%, p = 0.15), arterial patency (85% vs. 77%, p = 0.17), and ST-segment resolution (median 71% vs. 61%, p = 0.08) but was associated with more major hemorrhage (7.6% vs. 2.5%, p = 0.14) and transfusions (13.4% vs. 4.2%, p = 0.02). Intracranial hemorrhage occurred in 1.0%, 0.6%, and 1.7% of patients treated with any combination, eptifibatide 180/2/180 and half-dose TNK, and TNK monotherapy, respectively. CONCLUSIONS: Double-bolus eptifibatide (180/2/180) plus half-dose TNK tended to improve angiographic flow and ST-segment resolution compared with TNK monotherapy but was associated with more transfusions and non-cerebral bleeding. Further study is needed before this combination can be recommended for general use.