Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac outpu...

Regulation of Coronary Blood Flow During Exercise

Physiological studies have long documented the key role played by the autonomic nervous system in modulating cardiovascular functions and in controlling blood pressure values, both at rest and in response to environmental stimuli. Experimental and clinical investigations have tested the hypothesis that the origin, progression, and outcome of human hypertension are related to dysfunctional autonomic cardiovascular control and especially to abnormal activation of the sympathetic division. Here, we review the recent literature on the adrenergic and vagal abnormalities that have been reported in essential hypertension, with emphasis on their role as promoters and as amplifiers of the high blood pressure state. We also discuss the possible mechanisms underlying these abnormalities and their importance in the development and progression of the structural and functional cardiovascular damage that characterizes hypertension. Finally, we examine the modifications of sympathetic and vagal cardiovascular influences induced by current nonpharmacological and pharmacological interventions aimed at correcting elevations in blood pressure and restoring the normotensive state.

The Autonomic Nervous System and Hypertension

Background—Myocardial ischemia and infarction impair baroreflex sensitivity (BRS), which when depressed is predictive of future cardiac events after myocardial infarction (MI). The main objective of this study was to determine whether exercise training improves BRS in patients with coronary artery disease. Methods and Results—Ninety-seven male patients with and without a previous MI were recruited after myocardial revascularization surgery and randomized into trained (TR) or untrained (UTR) groups. TR patients underwent a residential exercise program at 85% of maximum heart rate (HRmax) consisting of 2 daily sessions 6 times a week for 2 weeks. Eighty-six patients (45 TR and 41 UTR) completed the study. BRS was assessed at baseline and at the end of the protocol by the spontaneous baroreflex method. The standard deviation of mean R-R interval (RRSD) was also assessed as a measure of heart rate variability. At baseline, there were no significant differences between TR and UTR patients in any variable. In T...

Effects of a residential exercise training on baroreflex sensitivity and heart rate variability in patients with coronary artery disease: A randomized, controlled study.

The sympathetic nervous system (SNS) is known to play a pivotal role in short- and long-term regulation of different functions of the cardiovascular system. In the past decades increasing evidence demonstrated that sympathetic neural control is involved not only in the vasomotor control of small resistance arteries but also in modulation of large artery function. Sympathetic activity and vascular function, both of which are key factors in the development and prognosis of cardiovascular events and disease, are linked at several levels. Evidence from experimental studies indicates that the SNS is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, such as nitric oxide (NO), reactive oxygen species (ROS), endothelin (ET), the renin-angiotensin system. Additionally, there is indirect evidence of a reciprocal relationship between endothelial function and activity of the SNS. A number of cardiovascular risk factors and diseases are characterized both by increased sympathetic outflow and decreased endothelial function. In healthy subjects, muscle sympathetic nerve activity (MSNA) appears to be related to surrogate markers of endothelial function, and an acute increase in sympathetic activity has been associated with a decrease in endothelial function in healthy subjects. However, direct evidence of a cause-effect relationship from human studies is scanty. In humans large artery stiffness has been associated with increased sympathetic discharge, both in healthy subjects and in renal transplant recipients. Peripheral sympathetic discharge is also able to modulate wave reflection. On the other hand, large artery stiffness can interfere with autonomic regulation by impairing carotid baroreflex sensitivity.

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Sympathetic regulation of vascular function in health and disease.

BACKGROUND Thrombotic complications occurring during coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) are relatively frequent and can be influenced by the type of radiographic contrast media used. Low osmolar contrast media (LOCM), both ionic and nonionic, have been considered to be safer than the older high osmolar contrast media (HOCM), causing less haemodynamic and symptomatic side effects. Recently, however, nonionic LOCM have been associated with an increased incidence of thrombotic events, including coronary occlusion and stroke.

METHODS AND RESULTS The effects of commonly used contrast media on platelets in native blood were investigated using immunolabeling and flow cytometry to detect platelet activation in vitro. A nonionic LOCM (Omnipaque) caused profound platelet degranulation in nearly 80% of platelets compared with 2 to 3% of platelets in the control. Conversely, an ionic HOCM (Urografin) caused only 25% degranulation, whereas an ionic LOCM (Hexabrix) caused no platelet activation and, furthermore, it inhibited the effects of thrombin on platelets. Platelet degranulation, quantified by immunolabeling, was paralleled by release of beta-thromboglobulin and platelet factor 4 from platelet alpha-granules. Blood from patients anticoagulated with heparin and pretreated with standard-dose aspirin in preparation for PTCA showed the same pattern of contrast media-induced platelet activation as normal subjects.

CONCLUSIONS These results suggest that the type of contrast media used during invasive imaging of the vasculature could have a significant effect on platelets. Platelet degranulation within a PTCA-damaged vessel would be increased by a nonionic contrast medium, releasing procoagulant molecules and platelet-derived growth factors into the damaged vessel lumen, which might contribute to acute thrombosis and the initiation of the restenosis process.

Profound platelet degranulation is an important side effect of some types of contrast media used in interventional cardiology.

Background In humans with coronary artery disease, ACE inhibition attenuates coronary sympathetic vasoconstriction. Whether this is due to removal of angiotensin (Ang) II production or to a reduced bradykinin breakdown, however, is unknown. Methods and Results In eight normotensive patients with angiographic evidence of mild left coronary artery lesions (≤50%), mean arterial pressure (MAP, intra-arterial catheter), heart rate (HR, ECG lead), coronary sinus blood flow (CBF, thermodilution method), and coronary vascular resistance (CVR, ratio between MAP and CBF) were measured before and during a 15-minute left intracoronary infusion of Ang II at a dose that had no direct coronary or systemic vasomotor effects. The same measurements were made before and during a 15-minute infusion of saline. A 2-minute cold pressor test (CPT) and a 45-second diving were performed at the end of either infusion period. These maneuvers were used because their coronary vasomotor effects are abolished by phentolamine and thus depend on sympathetic activation. During saline infusion, both CPT and diving caused a marked increase in MAP. HR increased with CPT and fell with diving. CBF increased in parallel to the MAP increase, with little change in CVR. The MAP and HR responses were similar during Ang II infusion, which, however, caused either no change or a reduction in CBF with a consequent marked increase in CVR with both CPT and diving. In four additional patients, the diameter of the stenotic vessels remained unchanged during the CPT performed under saline and Ang II infusion. Conclusions Ang II markedly enhances sympathetic influences on coronary circulation in humans, presumably by acting at the arteriolar level. This may explain the blunting effect of ACE inhibition on sympathetic coronary vasoconstriction in patients with coronary artery disease.

Intracoronary Angiotensin II Potentiates Coronary Sympathetic Vasoconstriction in Humans

Impairment of the arterial baroreflex during symptomatic and silent myocardial ischemia in humans.

The cold pressor test (CPT) is commonly used to determine the vasospastic origin of angina and to investigate the factors modulating coronary vasomotor tone. However, coronary vasoconstriction associated with this manoeuvre is often limited, particularly in patients with mild coronary atherosclerosis. To identfy stimuli that can more powerfully constrict the coronary arteries we compared the effects on coronary blood flow (thermodilution) and vascular resistance (mean aortic pressure divided by coronary blood flow) of CPT (2 min) and diving (D, 45 s) in subjects with angiographically documented mild (n = 11) or severe (n = 11) left anterior descending coronary artery stenosis. In subjects with severe coronary artery stenosis the rate-pressure product increased to a similar extent with CPT and D. The latter stimulus, however, caused a more marked fall in coronary blood flow and a much more pronounced increase in coronary resistance as compared to CPT (+44±3.1% vs + 19±1.6%, P<0.01). In the face of a similar increase in rate-pressure product, D caused a significant increase in coronary vascular resistance also in patients with mild coronary artery stenosis ( 50%) in which CPT failed to induce any coronary vasoconstriction (+ 16 ± 1.8% vs + 0.3 ± 1.3%. P <0.01). Thus, diving is a much more powerful coronary vasoconstrictor stimulus than CPT. It can thus replace CPT when an increase in coronary resistance is needed for diagnostic purposes or for investigating abnormalities in coronary vascular regulation.

Coronary response to diving in subjects with mild and severe left coronary artery disease.

Dihydropyridines (DHPs) exert a powerful coronary vasodilator action, but whether they actually affect the coronary vasomotor effects elicited by an increase in cardiac sympathetic drive is controversial. We assessed the effects of the DHP calcium antagonist amlodipine on coronary hemodynamics and vascular response to sympathetic activation in patients with coronary heart disease. In the control condition, mean arterial pressure (MAP, aortic catheter), heart rate (HR, ECG), rate-pressure product (RPP), coronary sinus blood flow (CBF, thermodilution) and coronary vascular resistance (CVR) (ratio between MAP and CBF) were measured in all our case series (13 patients with angiographically documented severe coronary artery disease) before and during a 2-min cold pressor test (CPT) and a 30-s diving (D) and, in the 8 patients of this case series who were smokers, also before and during smoking a cigarette (S, nicotine content 1.0 mg for 10 min). The same protocol used in control condition was repeated 30 min after intravenous (i.v.) bolus administration of 11 mg amlodipine. CPT, diving, and smoking increased MAP and RPP and caused a marked and significant increase in CVR (+12.1 +/- 4.8, +30.4 +/- 6.8, and +16.8 +/- 7.2%, respectively). Amlodipine reduced MAP, increased CBF, and caused a marked decrease in CBF. The drug did not modify responses to CPT and diving or pressure and HR responses to smoking, whereas the smoking-induced increase in coronary vascular resistance was attenuated after amlodipine administration (+3.2 +/- 2.7%, p < 0.05 vs. control condition). Thus, amlodipine does not attenuate the sympathetic coronary vasoconstrictor effects of CPT and diving.(ABSTRACT TRUNCATED AT 250 WORDS)

Rimini A

Papers

Intracoronary Angiotensin II Potentiates Coronary Sympathetic Vasoconstriction in Humans

Impairment of the arterial baroreflex during symptomatic and silent myocardial ischemia in humans.

Coronary response to diving in subjects with mild and severe left coronary artery disease.

Effects of amlodipine on coronary hemodynamics and vascular responses to sympathetic stimulation in patients with coronary heart disease