[Percutaneous coronary interventions. Guidelines of the European Society of Cardiology-ESC].
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Angioplasty, Balloon, Coronary↗
Biomedical subjects
Paolo G Camici
Publications and source records attributed to Paolo G Camici.
Abnormal myocardial presynaptic norepinephrine recycling in patients with Brugada syndrome.
BACKGROUND: Life-threatening ventricular tachyarrhythmias can occur in young patients without structural heart disease (idiopathic forms). In many patients, these are typically triggered by an increased sympathetic tone, eg, by physical or mental stress. In contrast, in Brugada syndrome, ventricular tachyarrhythmias more often occur during rest or sleep when the vagal tone is predominant. Furthermore, adrenergic agonists can reduce the level of ST-segment elevation, whereas it is increased by parasympathetic agonists or adrenergic antagonists. The aim of this study was to investigate presynaptic and postsynaptic myocardial sympathetic function in patients with Brugada syndrome. METHODS AND RESULTS: Nine patients with Brugada syndrome (6 male, 3 female; age, 41+/-13 years) were enrolled in this study. The cardiac autonomic nervous system was assessed noninvasively, quantifying myocardial presynaptic and postsynaptic sympathetic function by means of positron emission tomography with the norepinephrine analogue 11C-Hydroxyephedrine (11C-HED) and the nonselective beta-blocker 11C-CGP 12177 (11C-CGP). Presynaptic sympathetic norepinephrine recycling, assessed by 11C-HED, was globally increased in patients with Brugada syndrome compared with a group of age-matched healthy control subjects (92.9+/-16.2 mL/g versus 69.1+/-14.2 mL/g; P<0.05), whereas postsynaptic beta-adrenoceptor density, assessed by 11C-CGP, was similar in patients and control subjects (10.4+/-6.7 pmol/g versus 10.2+/-2.9 pmol/g; P=NS). CONCLUSIONS: The present study on autonomic innervation in Brugada syndrome describes an enhanced presynaptic norepinephrine recycling with preserved beta-adrenoceptor density, further supporting the hypothesis of an autonomic dysfunction in Brugada syndrome. This is a further step toward the understanding of the pathophysiology of the disease with potential future impact on therapeutic strategies.
Adult↗
Incidence of stunned, hibernating and scarred myocardium in ischaemic cardiomyopathy.
PURPOSE: Different criteria to identify residual viability in chronically dysfunctioning myocardium in patients with coronary artery disease (CAD) can be derived by the combined assessment of myocardial blood flow (MBF) and glucose utilisation (MRG) using positron emission tomography (PET). The aim of this study was to evaluate, in a large number of patients, the prevalence of these different patterns by purely quantitative means. METHODS: One hundred and sixteen consecutive patients with ischaemic cardiomyopathy (LVEF < or =40%) underwent resting 2D echocardiography to assess regional contractile function (16-segment model). PET with 15O-labelled water (H2 15O) and 18F-fluorodeoxyglucose (FDG) was used to quantify MBF and MRG during hyperinsulinaemic euglycaemic clamp. Dysfunctional segments with normal MBF (> or =0.6 ml min(-1) g(-1)) were classified as stunned, and segments with reduced MBF (<0.6 ml min(-1) g(-1)) as hibernating if MRG was > or =0.25 micromol min(-1) g(-1). Segments with reduced MBF and MRG <0.20 micromol min(-1) g(-1) were classified as transmural scars and segments with reduced MBF and MRG between 0.20 and 0.25 micromol min(-1) g(-1) as non-transmural scars. RESULTS: Eight hundred and thirty-four (46%) segments were dysfunctional. Of these, 601 (72%) were chronically stunned, with 368 (61%) having normal MRG (0.47+/-0.20 micromol min(-1) g(-1)) and 233 (39%) reduced MRG (0.16+/-0.05 micromol min(-1) g(-1)). Seventy-four (9%) segments with reduced MBF had preserved MRG (0.40+/-0.18 micromol min(-1) g(-1)) and were classified as hibernating myocardium. In addition, 15% of segments were classified as transmural and 4% as non-transmural scar. The mean MBF was highest in stunned myocardium (0.95+/-0.32 ml min(-1) g(-1)), intermediate in hibernating myocardium and non-transmural scars (0.47+/-0.09 ml min(-1) g(-1) and 0.48+/-0.08 ml min(-1) g(-1), respectively), and lowest in transmural scars (0.40+/-0.14 ml min(-1) g(-1), P<0.01). MRG was comparable in hibernating and stunned myocardium with preserved MRG (0.40+/-0.19 micromol min(-1) g(-1) vs 0.46+/-0.20 micromol min(-1) g(-1), NS), and lowest in stunned myocardium with reduced MRG and transmural scars. CONCLUSION: Chronic stunning is more prevalent than expected. The degree of MRG reduction in stunned myocardium may disclose segments at higher risk of permanent damage.
Cardiomyopathies↗
Systemic inhibition of nitric oxide synthase unmasks neural constraint of maximal myocardial blood flow in humans.
BACKGROUND: Nitric oxide (NO) is an endothelial mediator that regulates vascular smooth muscle tone, but it may exert its cardiovascular action also by modulating the autonomic control of vasomotor tone. We assessed the effect of simultaneous inhibition of both endothelial (eNOS) and neuronal (nNOS) NO synthase isoforms on myocardial blood flow (MBF) and coronary flow reserve (CFR) in volunteers and in (denervated) transplant recipients. METHODS AND RESULTS: MBF (mL x min(-1) x g(-1)) was measured at rest and during adenosine-induced hyperemia with positron emission tomography and 15O-labeled water. CFR was calculated as adenosine/resting MBF. Measurements were repeated during one of the following intravenous infusions: group 1 (n=12), saline; group 2 (n=9), 3 mg/kg N(G)-monomethyl-L-arginine (L-NMMA), which crosses the blood-brain barrier and inhibits both eNOS and nNOS; group 3 (n=13), 10 mg/kg L-NMMA; group 4 (n=8), phenylephrine titrated to simulate the hemodynamic changes in group 3; and group 5 (n=6), 10 mg/kg L-NMMA infused into the heart transplant recipients. After intervention, hyperemic MBF and CFR were unchanged in groups 1, 2, and 4. By contrast, both hyperemic MBF (+53%, P<0.0001 versus baseline) and CFR (+52%, P<0.0001 versus baseline) increased in group 3, whereas they remained unchanged in group 5, which suggests that an intact cardiac innervation was required for the increase in MBF and CFR observed in group 3. CONCLUSIONS: The results of the present study suggest that maximal adenosine-induced hyperemia and CFR in humans are constrained by neurally mediated vasoconstriction, which can be relieved by systemic NOS inhibition with L-NMMA.
Adenosine↗
Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia.
PURPOSE: Tetrahydrobiopterin (BH4) is an essential co-factor for the synthesis of nitric oxide (NO), and BH4 deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH4 deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia. METHODS: Myocardial blood flow (MBF; ml min(-1) g(-1)) was measured at rest, during adenosine-induced (140 microg kg(-1) min(-1) over 7 min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using 15O-labelled water and positron emission tomography. Measurements were repeated 60 min later, after intravenous infusion of BH4 (10 mg kg(-1) body weight over 30 min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress. RESULTS: BH4 increased exercise-induced hyperaemia in controls (2.96+/-0.58 vs 3.41+/-0.73 ml min(-1) g(-1), p<0.05) and hypercholesterolaemic subjects (2.47+/-0.78 vs 2.70+/-0.72 ml min(-1) g(-1), p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52+/-1.10 vs 4.85+/-0.45 ml min(-1) g(-1), p=NS) or hypercholesterolaemic subjects (4.86+/-1.18 vs 4.53+/-0.93 ml min(-1) g(-1), p=NS). Flow reserve utilisation remained unchanged in controls (70+/-17% vs 71+/-19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53+/-15% vs 66+/-14%, p<0.05). CONCLUSION: BH4 restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH4 deficiency may contribute to coronary microcirculatory dysfunction in hypercholesterolaemia.
Adult↗
Program of cell survival underlying human and experimental hibernating myocardium.
Hibernating myocardium refers to chronically dysfunctional myocardium in patients with coronary artery disease in which cardiac viability is maintained and whose function improves after coronary revascularization. It is our hypothesis that long-term adaptive genomic mechanisms subtend the survival capacity of this ischemic myocardium. Therefore, the goal of this study was to determine whether chronic repetitive ischemia elicits a gene program of survival protecting hibernating myocardium against cell death. Accordingly, we measured the expression of survival genes in hibernating myocardium, both in patients surgically treated for hibernation and in a chronic swine model of repetitive ischemia reproducing the features of hibernation. Human hibernating myocardium was characterized by an upregulation of genes and corresponding proteins involved in anti-apoptosis (IAP), growth (VEGF, H11 kinase), and cytoprotection (HSP70, HIF-1alpha, GLUT1). In the swine model, the same genes and proteins were upregulated after repetitive ischemia, which was accompanied by a concomitant decrease in myocyte apoptosis. These changes characterize viable tissue, because they were not found in irreversibly injured myocardium. Our report demonstrates a novel mechanism by which the activation of an endogenous gene program of cell survival underlies the sustained viability of the hibernating heart. Potentially, promoting such a program offers a novel opportunity to salvage postmitotic tissues in conditions of ischemia.
Adult↗
Is central nervous system processing altered in patients with heart failure?
AIMS: Breathlessness is a cardinal symptom of heart failure and the altered regulation of breathing is common. The contribution of abnormal central nervous system activity has not previously been investigated directly, although abnormal autonomic responses have been described. Our aim was to assess whether heart failure patients exhibit different patterns of regional brain activation after exercise stress. METHODS: We used positron emission tomography with H2(15)O, to measure changes in regional cerebral blood flow (rCBF) and absolute global cerebral blood flow (gCBF) in 6 male class II/III heart failure patients and 6 normal controls. Breathlessness (0-5 visual analogue scale) and respiratory parameters were measured at rest, after horizontal bicycle exercise and during isocapnic hyperventilation. CBF was measured in each condition in all subjects. RESULTS: Both groups were similarly breathless after exercise and the respiratory parameters were comparable. rCBF differences for the main comparison (exercise vs hyperventilation) were: activation of the right frontal medial gyrus (P < 0.001, Z = 4.90) and left precentral gyrus (P < 0.03, Z = 4.66) in controls but not in patients. Both groups had rCBF increases in the left anterior cingulate (P < 0.05, Z = 4.67) and right dorsal cingulate cortex (P < 0.05, Z = 4.66). The gCBF did not differ between exercise, isocapnic hyperventilation and rest in patients but, in controls, gCBF was greater after exercise compared to either isocapnic hyperventilation or rest. CONCLUSION: Heart failure patients had a distinct pattern of regional cortical activity with exercise-induced breathlessness but unvarying CBF values between conditions. These central neural differences in activity may contribute to some features of heart failure, such as variability in symptoms and autonomic dysregulation.
Aged↗
Effect of left ventricular assist device combination therapy on myocardial blood flow in patients with end-stage dilated cardiomyopathy.
BACKGROUND: Changes in myocardial blood flow (MBF) and coronary flow reserve (CFR) are independent prognostic risk factors in idiopathic dilated cardiomyopathy (DCM). The aim of this study was to assess the impact of left ventricular unloading using left ventricular assist device (LVAD) combination therapy on resting MBF and CFR in patients with end-stage heart disease. METHODS: We studied 11 patients with deteriorating end-stage DCM (New York Heart Association Class 4) treated with LVAD support combined with pharmacologic therapy in a recovery program. Absolute MBF was measured using oxygen-15-labeled water (H(2)(15)O) positron emission tomography (PET) at rest during LVAD support and 15 minutes after the LVAD was switched off. Data were corrected for rate pressure product (RPP) when appropriate. Hyperemic MBF (intravenous adenosine, 140 mug/kg . min) was also measured in 6 patients with the LVAD switched off. CFR was calculated as the ratio MBF adenosine/MBF LVAD off (corrected). Data are expressed as mean +/- SD. RESULTS: At 317 +/- 193 days after device implantation, resting MBF was 0.95 +/- 0.29 (LVAD on) and 1.46 +/- 0.62 (LVAD off, corrected) ml/min . g (p = 0.01). MBF (LVAD on) was comparable with that of 11 age- and gender-matched normal controls (1.09 +/- 0.22 ml/min . g). CFR in the LVAD group was 1.49 +/- 0.99 compared with 3.56 +/- 1.42 in normal controls (p < 0.01). CONCLUSIONS: During LVAD support, resting MBF (LVAD on) was comparable to MBF in normal controls and increased when the LVAD was switched off. However, CFR was significantly impaired, even though all patients studied showed varying degrees of myocardial recovery. The implications of these findings, particularly in the long term, require further study.
Adolescent↗
The contribution of hibernation to heart failure.
For many years the functional sequelae of chronic coronary artery disease (CAD) were considered irreversible. Evidence accrued over the past three decades proves that this concept is not necessarily true. Non-randomised studies demonstrated that coronary revascularisation (CR) confers symptomatic and prognostic benefits to patients with CAD and heart failure. Based on available studies, one can assume that the beneficial effect of CR in heart failure derives primarily from recovery of contractile function in 'hibernating myocardium' (HM), i.e., chronically dysfunctional, but viable, myocardium subtended by stenosed coronary arteries which recovers after CR. Cardiac imaging with echocardiography, single photon and positron emission tomography (PET) and magnetic resonance allows the identification of HM. These techniques have comparable predictive values in patients with moderate left ventricular impairment. PET studies have shown that resting myocardial blood flow is preserved in most cases of HM while its main feature is a severe impairment of coronary flow reserve. Thus, the pathophysiology of HM is more complex than initially postulated. Recent evidence that repetitive ischaemia in patients can be cumulative and lead to more severe and prolonged stunning, lends further support to the hypothesis that, at least initially, stunning and HM are two facets of the same coin.
Coronary Artery Disease↗
Coronary microvascular dysfunction and ischemia in hypertrophic cardiomyopathy. Mechanisms and clinical consequences.
Symptoms and signs of myocardial ischemia are often found in patients with hypertrophic cardiomyopathy (HCM) despite angiographically normal coronary arteries. Myocardial ischemia is deemed responsible for some of the lethal complications of HCM including ventricular arrhythmias, sudden death, progressive left ventricular remodeling, and systolic dysfunction. In the past decade, a number of studies using positron emission tomography have demonstrated severe impairment of the vasodilator response to dipyridamole in the majority of HCM patients, not only in the hypertrophied septum but also in the non-hypertrophied left ventricular free wall. In the absence of coronary stenoses, this finding is indicative of diffuse microvascular dysfunction, in line with the autoptic evidence of widespread abnormalities of the intramural coronary arterioles. In turn, microvascular dysfunction represents a very likely substrate for recurrent ischemia. This may account for the fact that microvascular dysfunction has recently been shown to represent an early and powerful predictor of an unfavorable outcome in HCM. The aim of this article is to provide a concise overview of the available evidence of microvascular dysfunction and ischemia in HCM, and to speculate on the potential implications for management.
Cardiomyopathy, Hypertrophic↗
Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy.
BACKGROUND: Microvascular dysfunction, reflected by an inadequate increase in myocardial blood flow in response to dipyridamole infusion, is a recognized feature of hypertrophic cardiomyopathy. Its long-term effect on the prognosis is unknown. We prospectively evaluated a cohort of patients with hypertrophic cardiomyopathy after they had undergone quantitative assessment of myocardial blood flow by positron-emission tomography (PET). METHODS: Fifty-one patients (New York Heart Association class I or II) were followed for a mean (+/-SD) of 8.1+/-2.1 years after PET. Twelve subjects with atypical chest pain served as controls. Measurement of flow was performed at base line and after the infusion of the coronary vasodilator dipyridamole, with the use of nitrogen-13-labeled ammonia. Patients were then divided into three equal groups with increasing values of myocardial blood flow. RESULTS: The response of myocardial blood flow to dipyridamole was severely blunted in the patients, as compared with the controls (1.50+/-0.69 vs. 2.71+/-0.94 ml per minute per gram of tissue, P<0.001). Sixteen patients (31 percent) had an unfavorable outcome (death from cardiovascular causes, progression to New York Heart Association class III or IV, or sustained ventricular arrhythmias requiring the implantation of a cardioverter-defibrillator) 2.2 to 9.1 years after PET. Reduced blood flow in response to dipyridamole was strongly associated with an unfavorable outcome. Multivariate analysis showed that among patients in the lowest of the three flow groups the age-adjusted relative hazard of death from cardiovascular causes was 9.6 (P=0.02) and the relative hazard of an unfavorable outcome (a combined end point) was 20.1 (P=0.003), as compared with patients in the two other flow groups. Specifically, all four patients who died from heart failure and three of five who died suddenly were in this subgroup. CONCLUSIONS: In patients with hypertrophic cardiomyopathy, the degree of microvascular dysfunction is a strong, independent predictor of clinical deterioration and death. Severe microvascular dysfunction is often present in patients with mild or no symptoms and may precede clinical deterioration by years.
Adult↗
Functional changes in coronary microcirculation after valve replacement in patients with aortic stenosis.
BACKGROUND: Increased extravascular compression and reduced diastolic perfusion time (DPT), rather than vascular remodeling, influence coronary microcirculatory dysfunction in aortic stenosis (AS). However, alterations after aortic valve replacement (AVR) remain unclear. The aim of the present study was to quantify changes in transmural perfusion and coronary vasodilator reserve (CVR), a measure of microcirculatory function, after AVR and determine the relative contribution of left ventricular mass (LVM) regression, change in aortic valve area (AVA), and DPT. METHODS AND RESULTS: Twenty-two patients with AS were studied before and 1 year after AVR using echocardiography to measure AVA, cardiovascular magnetic resonance to assess LVM, and positron emission tomography to quantify resting and hyperemic myocardial blood flow (MBF) and CVR. Regression of LVM occurred in all patients (from 129+/-30 to 94+/-24 g/m2; P<0.0001), and there was a significant reduction in resting MBF and increase in CVR corrected for rate-pressure product after AVR, although these changes displayed marked heterogeneity. Regression of LVM was linearly related to change in resting total LV blood flow but not CVR. Increase in hyperemic MBF and CVR transmurally was directly related to the increase in AVA after AVR. A significant relationship existed between the change in hyperemic DPT (1.0+/-4.7 s/min [range, 6.8 to 9.6]) and change in transmural CVR (y=0.08x+0.18; r=0.44; P=0.04). CONCLUSIONS: Changes in coronary microcirculatory function in patients with AS after AVR are not directly dependent on regression of LVM. Reduced extravascular compression and increased DPT are proposed as the main mechanisms for improvement in MBF and CVR after AVR.
Adult↗
Pathophysiology and diagnosis of hibernating myocardium in patients with post-ischemic heart failure: the contribution of PET.
Identification and treatment of hibernating myocardium (HM) lead to improvement in LV function and prognosis in patients with post-ischemic heart failure. Different techniques are used to diagnose HM: echocardiography, MRI, SPECT and PET and, in patients with moderate LV impairment, their predictive values are similar. There are few data on patients with severe LV dysfunction and heart failure in whom the greatest benefits are apparent after revascularization. Quantification of FDG uptake with PET during hyperinsulinemic euglycemic clamp is accurate in these patients with the greatest mortality risk in whom other techniques may give high false negative rates. The debate on whether resting myocardial blood flow to HM is reduced or not has stimulated new research on heart failure in patients with coronary artery disease. PET with H2(15)O or 13NH3 has been used for the absolute quantification of regional blood flow in human HM. When HM is properly identified, resting blood flow is not different from that in healthy volunteers although a reduction of approximately 20% can be demonstrated in a minority of cases. PET studies have shown that the main feature of HM is a severe impairment of coronary vasodilator reserve that improves after revascularization in parallel with LV function. Thus, the pathophysiology of HM is more complex than initially postulated. The recent evidence that repetitive ischemia in patients can be cumulative and lead to more severe and prolonged stunning, lends further support to the hypothesis that, at least initially, stunning and HM are two facets of the same coin.
Blood Flow Velocity↗
Myocardial blood flow in patients with hibernating myocardium.
The debate on whether resting myocardial blood flow (MBF) to hibernating myocardium is reduced or not has attracted a lot of interest and has contributed to stimulate new research on heart failure in patients with coronary artery disease (CAD). Positron emission tomography with oxygen-15 labeled water (H(2)(15)O) or nitrogen-13 labeled ammonia (13NH(3)) has been used for the absolute quantification of regional MBF in human hibernating myocardium. When hibernating myocardium is properly identified, i.e. a dysfunctional segment subtended by a stenotic coronary artery that improves function upon reperfusion, the following conclusions can be reached based on the available literature: (a) in the majority of these studies resting MBF in hibernating myocardium is not different from either flow in remote tissue in the same patient or MBF in normal healthy volunteers; (b) a reduction in MBF of approximately 20% compared to MBF in remote myocardium or age matched normal subjects has been demonstrated in a minority of truly hibernating segments; (c) hibernating myocardium is characterized by a severely impaired coronary flow reserve which improves after revascularization in parallel with contractile function. Thus, the pathophysiology of hibernation in humans is more complex than initially postulated. The recent evidence that repetitive ischemia in patients with coronary artery disease can be cumulative and lead to more severe and prolonged stunning, lends further support to the hypothesis that, at least initially, stunning and hibernation are two facets of the same coin.
Animals↗
Hibernation and congestive heart failure.
The most common cause of heart failure is coronary artery disease, and whilst intensive treatment of acute coronary syndromes and myocardial infarction continue to reduce the mortality associated with these conditions, many survivors develop heart failure. In general, heart failure secondary to ischaemic heart disease results from: (i) irreversible myocyte loss due to infarction with scar formation; (ii) chronic left ventricular dysfunction which may recover after revascularisation (hibernating myocardium); (iii) changes in remote myocardium (adverse remodelling). A number of studies suggest that patients with post-ischaemic heart failure may derive symptomatic and prognostic benefit from coronary revascularisation and most of this benefit is thought to derive from functional improvement of hibernating myocardium. Although the mechanisms of hibernation remain poorly understood, studies with positron emission tomography have shown that blood flow to hibernating myocardium is usually within or only slightly below the normal range whilst the coronary vasodilator reserve is always severely reduced and the concept that stunning and hibernation may be causally related has gained support in recent years. There is increasing consensus amongst clinicians regarding the importance of identifying and treating hibernating myocardium in patients with coronary artery disease and heart failure, and a randomised study comparing optimum medical treatment to optimum medical treatment with complete revascularisation has just commenced in the United Kingdom (HEART-UK) and will provide guidance regarding diagnosis and treatment of these patients.
Angiotensin-Converting Enzyme Inhibitors↗
Improvement of impaired coronary vasodilator reserve in hypertensive patients by low-dose ACE inhibitor/diuretic therapy: a pilot PET study.
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Angiotensin-Converting Enzyme Inhibitors↗
Gated PET and ventricular volume.
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Animals↗
[Stunning, hibernation, and heart failure in patients with coronary disease: crucial role of impaired coronary flow reserve].
Hibernating myocardium can be defined as a chronic, but reversible left ventricular dysfunction that may contribute to congestive heart failure in patients with coronary artery disease. The dysfunction can improve after coronary revascularization and therefore its identification and treatment become central in the management of patients with heart failure secondary to coronary artery disease. Hibernating myocardium can be detected by several techniques (echocardiography performed during the infusion of dobutamine, single photon and positron emission tomography-PET, and magnetic resonance imaging), but none of these techniques can be considered unequivocally superior to the others for the identification of hibernating myocardium. As PET technology has advanced, the noninvasive quantification of absolute regional myocardial blood flow has become possible. The measurement of myocardial blood flow by PET has contributed to the demonstration that transmural blood flow in hibernating muscle is generally within the normal range while the coronary flow reserve is invariably and severely impaired. These findings have contributed to a new pathophysiological theory of hibernation where repetitive ischemia and stunning are considered as the initial mechanisms that might start the process of myocardial hibernation.
Animals↗