Myocardial Vascular Resistance Research Articles

Persistent Coronary Vasomotor Tone During Myocardial Ischemia Occurs at the Capillary Level and May Involve Pericytes.

BackgroundThere is persistent coronary vasomotor tone during myocardial ischemia, despite ongoing coronary arteriolar dilatation. The mechanism underlying this vasodilatory tone, which can be unmasked by coronary vasodilators, is unclear. We hypothesized that persistent microvascular resistance during myocardial ischemia occurs at the level of capillaries and may be caused by pericytes.MethodsWe studied nine instrumented dogs where coronary blood flow and coronary driving pressure were reduced to half by placement of stenoses. Myocardial blood flow and myocardial blood volume were measured with myocardial contrast echocardiography before and during adenosine administration. In three animals, the heart was perfusion-fixed under these conditions for electron microscopic assessment of capillary and pericyte size.ResultsDuring ischemia, myocardial blood volume decreased and myocardial vascular resistance remained unchanged. Adenosine administration reversed the decline in myocardial blood volume and decreased myocardial vascular resistance. Electron microscopy showed larger capillaries in ischemic beds receiving adenosine than ischemic beds not receiving adenosine. Pericytes in beds receiving adenosine also tended to be larger.ConclusionCapillaries are the site of persistent vasomotor tone during myocardial ischemia; any other site of vascular regulation (arterioles or venules) cannot explain these myocardial contrast echocardiography findings, which are confirmed on post-mortem electron microscopic examination. The decrease in capillary size is likely caused by pericyte contraction in an attempt to maintain a constant capillary hydrostatic pressure. Adenosine relaxes pericytes, restores myocardial blood volume, reduces myocardial vascular resistance, and improves regional function during ischemia. These findings could have important therapeutic implications.

Perinatal maternal undernutrition does not result in offspring capillary rarefaction in the middle-aged male baboon at rest.

Microvascular health is a main determinant of coronary blood flow reserve and myocardial vascular resistance. Extracardiac capillary abnormality has been reported in subjects at increased coronary heart disease risk, such as prehypertension, hypertension, diabetes, hyperlipidemia, and atherosclerosis. We have reported cardiovascular dysfunction in a cohort of maternal nutrient reduction (MNR)-induced intrauterine growth restriction (IUGR) baboon offspring. Here we test the hypothesis that there is oral capillary rarefaction associated with MNR-induced IUGR. Capillary density was quantified using in vivo high-power capillaroscopy on seven middle-aged (~10.7 yr; human equivalent ~40 yr) male IUGR baboons and seven male age-matched controls in the lateral buccal and inferior labial mucosa. While no difference was found between groups in either area by fraction area or optical density for these vascular beds derived from fetal preductal vessels, further studies are needed on post-ductal vascular beds, retina, and function.

The Variation of Hemodynamic Parameters Through PiCCO in the Early Stage After Severe Burns.

To investigate early hemodynamics of severely burned patients via PiCCO and to discuss clinical significance of hemodynamic monitoring for burn shock resuscitation, 55 extensive burn patients were enrolled in this retrospective study. The fluid resuscitation was guided according to Chinese General Formula and adjusted with urinary output of 0.5-1.0 ml/h/kg as a resuscitation goal. All patients were diagnosed within a relatively stable condition during burn shock stage, and they received PiCCO monitoring within 6 hours after burn. The preload parameter intrathoracic blood volume index was low at first, then returned to normal. The flow parameter cardiac index and myocardial contractility parameter dPmax were gradually changed from low level in the early stage to high level in the fluid reabsorption stage. The afterload parameter systemic vascular resistance index had completely opposite tendency. The lung-related parameters extravascular lung water index and pulmonary vascular permeability index were roughly in the normal range. The change of cardiac index had a linear regression relationship with dPmax and systemic vascular resistance index but had no significant relationship with intrathoracic blood volume index. Under effective fluid resuscitation, the early hemodynamics after burn is still in dynamically changing status, characterized as transition from low cardiac output (CO)-high vascular resistance in early shock stage to high CO-low vascular resistance in fluid reabsorption stage. CO mainly depends on the myocardial contractility and vascular resistance, but not on the blood volume. Excessive fluid resuscitation cannot get normal CO. The normal value of hemodynamics cannot be used as end point of burn shock resuscitation. Dynamic observation of hemodynamics is of great importance.

A Painful Sleep Apnea

Background: Obstructive sleep apnea (OSA) is largely recognized as an independent risk factor for coronary artery disease (CAD), its prevalence is higher in the acute phase of ischemic heart disease and the risk of developing ischemic myocardial injury is greater in presence of this syndrome. OSA seems to exacerbate ischemic nocturnal events, to impair coronary blood flow (CBF) response to myocardial energy demand, to increase myocardial vascular resistance and to negatively impact outcomes of percutaneous coronary intervention (PCI) Case report: We reported the case of 57-years-old men with multiples cardiovascular risk factors and previous history of severe CAD, who presented multiples relapses of in-stent restenosis and failure in percutaneous procedures; because of overweight, snoring and nocturnal pains referred occurring simultaneously of respiratory apneic events, he underwent to an overnight sleep screening, resulting positive for obstructive sleep apnea. Conclusions: OSA, likewise others chronic inflammatorystates, could be responsible for negative outcomes of PCI(in-stent proliferation restenosis) due to abnormal inflammatory state, coronary microvascular dysfunction secondary to vascular remodeling, and thusineffectiveness of coronary blood flow (CBF) response to myocardial work.

Intracoronary administration of nicorandil during primary percutaneous coronary intervention: Impact on restoration of regional myocardial perfusion in reperfused myocardium during the subacute phase of myocardial infarction

BackgroundThe impact of nicorandil as adjunctive therapy for percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) is controversial. We performed 15O-labeled water positron emission tomography (PET) to quantify regional myocardial perfusion in patients with STEMI who received nicorandil or no adjunctive therapy during PCI. MethodsPCI was performed within 8h after STEMI onset in 33 patients. 14 patients received intracoronary nicorandil 2mg immediately after recanalization of the culprit lesion (Nico group). After 3–4weeks, PET was performed in which myocardial blood flow (MBF) was measured at baseline and during adenosine triphosphate (ATP)-induced hyperemia. Myocardial vascular resistance (MVR) was calculated for all segments. Data were obtained from the reperfused (Rep) and normal segments (Cont) in each patient. ResultsIn patients not given nicorandil (No-Nico group), the MBF was significantly lower in Rep than that in Cont at baseline and during hyperemia (Cont vs. Rep: 0.82±0.14 vs. 0.68±0.11, P=0.001, ATP-Cont vs. ATP-Rep: 2.00±0.72 vs. 1.52±0.61, P=0.017), which was restored in the Nico group (Cont vs. Rep: 0.79±0.17 vs. 0.78±0.20; ATP-Cont vs. ATP-Rep: 2.02±0.84 vs. 1.84±0.62). MVR was elevated in Rep at baseline and during hyperemia in the No-Nico group. MVR elevation in Rep was prevented in the Nico group. Conclusions15O-labeled water PET was feasible for segmental analysis of MBF during the subacute phase of STEMI. It revealed that intracoronary administration of nicorandil to STEMI patients who underwent PCI prevented MVR elevation and thus restored MBF in the reperfused segments to a level similar to that in the normal segments.

Anaesthesia for repair of anomalous origin of left coronary artery from pulmonary artery.

Sir, Anomalous origin of left coronary artery from pulmonary artery (ALCAPA) is a rare congenital heart defect (1 in 3,00,000 live births), in which left coronary artery arises from pulmonary artery, instead of branching from the aorta.[1,2,3] A 35-year-old, 47 kg female was scheduled for corrective surgical repair of ALCAPA. For the previous 2 years, she had progressively increasing breathlessness and anginal attacks on exertion. The 12 lead electrocardiograms (ECG) revealed sinus rhythm, without any ST or T wave changes. Transthoracic echocardiography revealed mild left ventricular enlargement and normal ejection fraction of 55%, without any regional wall motion abnormalities. The coronary angiography revealed ALCAPA. Her medications included enalapril, digoxin and furosemide. In the operation theatre, after securing a 16 gauge intravenous (IV) cannula, monitoring with ECG, non-invasive blood pressure (BP), cardiac output (CO) and oxygen saturation (SpO2) was started. The left femoral artery and left radial artery were cannulated for invasive BP monitoring. General anaesthesia was induced and trachea intubated using fentanyl 100 μg, morphine 6 mg, midazolam 2 mg, etomidate 6 mg and vecuronium 8 mg (all administered IV). Right internal jugular vein was cannulated, and anaesthesia was maintained using oxygen/air/isoflurane, with infusions of rocuronium and fentanyl. The ventilatory settings were aimed to prevent hypocarbia, hyperoxia and alkalosis. A low FiO2 of 0.4 was used to maintain a high pulmonary vascular resistance (PVR). The end-tidal CO2 was maintained between 40 and 42 mmHg, and partial pressure of oxygen was monitored. The surgery was performed under cardiopulmonary bypass (CPB). Dopamine (5 μg/kg/min) was used during weaning of the patient from CPB. Intra-operatively and post-operatively, patient remained haemodynamically stable. The survival of neonates with ALCAPA varies with the adequacy of left ventricular perfusion. This depends on the inflow of blood to left coronary artery via collaterals from right coronary artery (RCA) and the proportion of coronary steal from left coronary artery to the pulmonary artery. Only 10-20% of these neonates survive till adulthood.[4] In the post-natal period, there is a decrease in pulmonary vascular resistance (PVR) and oxygen content of the pulmonary blood. This can reverse the direction of blood flow from left coronary artery to the pulmonary artery (coronary steal phenomenon). This causes hypo-perfusion of the left ventricular myocardium by relatively de-saturated blood, leading to myocardial ischaemia. This can lead to mitral valve insufficiency.[5,6] Patients might have accompanying atrial septal defect, ventricular septal defect, patent ductus arteriosus, tetralogy of Fallot or coarctation of the aorta. All these factors precipitate congestive heart failure in 80–90% of these infants. These neonates present with tachypnoea, tachycardia, poor feeding, irritability and diaphoresis. They can survive till adulthood, due to well-developed collaterals from RCA, which provides adequate perfusion to the left ventricle. The RCA was dilated and tortuous in this patient [Figure 1]. The coronary angiogram is the gold standard investigation for diagnosis of ALCAPA. The adults present with exertional dyspnoea, angina and cardiac arrhythmias.[2] Diuretics and inotropes are used for the management of congestive heart failure. Figure 1 Dilated and tortuous right coronary artery The anaesthetic goals are to (1) maintain optimum preload, (2) prevent a decrease in PVR, (3) maintain myocardial contractility, (4) maintain low or normal systemic vascular resistance (SVR) and (5) prevent tachycardia. The preload is optimized to ensure an adequate CO. In these patients, the stroke volume is monitored instead of CO, because CO varies with heart rate. The laryngoscopy/intubation should be smooth and rapid. Swings in heart rate and BP are avoided. Tachycardia is detrimental, as it can alter the myocardial oxygen supply/demand ratio and predispose to myocardial ischaemia. Etomidate being haemodynamically stable is preferred for induction of anaesthesia. Isoflurane is the inhalational agent of choice, as it causes less myocardial depression, compared with halothane or sevoflurane and is a better myocardial protective agent. Low PVR will accentuate the coronary steal phenomenon. The presence of hypocarbia, hyperoxia or alkalosis decreases PVR and is detrimental. They are ventilated using oxygen/air mixture, and partial pressure of oxygen is not allowed to rise very high. A higher end-tidal CO2 is maintained to achieve a higher PVR. A low afterload SVR is maintained, for an adequate stroke volume. Aggressive reduction of afterload may also be deleterious, as it attenuates the perfusion of RCA, thus decreasing the blood flow to left coronary artery. Inotropes such as dopamine, dobutamine or milrinone should be used cautiously, as they increase the consumption of myocardial oxygen, which may accentuate myocardial ischemia. Thus, patients with ALCAPA repair can be managed successfully, after understanding the pathophysiological changes.

Abstract 9608: Intracoronary Administration of Nicorandil During Direct Coronary Stenting Complements Restoration of Regional Perfusion at Subacute Phase of Myocardial Infarction: A Demonstration With O-15 Water Pet

Purpose: Controversies exist regarding the impact of nicorandil as the adjunctive therapy for direct coronary stenting in patients with ST elevation myocardial infarction (STEMI).Therefore, we performed O-15 water positron emission tomography (water PET) to quantify regional myocardial perfusion in patients with STEMI who received nicorandil or no adjunctive therapy during successful direct stenting. Methods: In 28 patients with STEMI (65+/-13 yrs: 22 males), direct stenting was performed within 8 hrs after the onset. Five of 28 patients who underwent successful direct stenting received intracoronary administration (i.c.) of nicorandil 4 mg immediately after the first recanalization of culprit lesion.At 3 to 4 weeks from the onset, water PET was performed in which myocardial blood flow (MBF) was measured at rest and during hyperemia and myocardial vascular esistance (MVR) was calculated. Data were obtained from both reperfused and normal control regions in each patient. Results: See Figure. In patients who did not receive nicorandil (No-Nico), MBF in reperfused area (Rep) was lower than that in normal control regions (Cont) both at rest and during hyperemia (ATP). However, in the nicorandil-treated patients, MBF in Rep was restored to the similar level of that in Cont both at rest and during ATP. MVR was elevated in Rep both at rest and during ATP in No-Nico patients; such elevation of MVR in Rep was successfully prevented in the nicorandil-treated patients. Conclusion: O-15 water-PET at subacute phase revealed that i.c.nicorandil during direct stenting successfully prevented the elevation of myocardial vascular resistance and thus, restored myocardial blood flow in reperfused areas to the similar level as that in non-infarcted regions in patients with STEMI.

Microcirculation and left-ventricular hypertrophy

Microcirculation and left-ventricular hypertrophy

Coronary Vasoreactivity in Subjects with Thyroid Autoimmunity and Subclinical Hypothyroidism Before and After Supplementation with Thyroxine

The association of subclinical hypothyroidism (SCH) with increased risk for cardiovascular disease is still controversial. This study aimed to examine coronary vascular reactivity by positron emission tomography (PET) in asymptomatic patients with SCH before and after levothyroxine (LT4) supplementation. Ten patients (7 women and 3 men; mean age 43±15 years) with untreated autoimmune SCH, defined by elevated levels of thyroid-stimulating hormone (mean TSH: 16.9±11.3 μU/mL), normal levels of free thyroxine (0.9±0.1 μg/mL), free triiodothyronine (3.2±0.4 pg/mL), and positive thyroid peroxidase antibodies were studied. Eight euthyroid subjects with similar low-risk cardiovascular risk profile served as controls. Myocardial blood flow (MBF) and coronary flow reserve (CFR) were quantitatively assessed with rest/stress N-13 ammonia PET at baseline and after 6 months of LT4 replacement therapy (given only to patients). At baseline, stress MBF and CFR corrected (c) for rate pressure product (RPP) and myocardial vascular resistance (MVR) during stress were significantly reduced in SCH compared with controls (stress MBF: 2.87±0.93 vs. 4.79±1.16 mL/g/min, p=0.003; CFR: 2.6±0.73 vs. 4.66±1.38, p=0.004; MVR: 40.14±18.76 vs. 20.47±6.24 mmHg/mL/min, p=0.02). Supplementation therapy with LT4 normalized TSH in all subjects and was associated with an increase in CFR (2.6±0.73 vs. 3.81±1.19, p=0.003) and with a tendency toward a decrease in MVR. Differences in CFR between SCH and controls were also seen after correction of resting MBF for RPP. In asymptomatic subjects with SCH due to thyroid autoimmunity, coronary microvascular function is impaired and improves after supplementation with LT4. This may partially explain the increased cardiovascular risk attributed to SCH.

Pioglitazone Attenuates Acute Cocaine Toxicity in Rat Isolated Heart

The authors tested whether cocaine depresses mitochondrial acylcarnitine exchange and if a drug that enhances glucose metabolism could protect against cocaine-induced cardiac dysfunction. Oxygen consumption with and without cocaine was compared in rat cardiac mitochondria using octanoylcarnitine (lipid) or pyruvate (nonlipid) substrates. Isolated hearts from rats with or without a pioglitazone-supplemented diet were exposed to cocaine. The 0.5 mM cocaine inhibited respiration supported by octanoylcarnitine (82 ± 10.4 and 45.7 ± 4.24 ngatomO min⁻¹ · mg⁻¹ · protein ± SEM, for control and cocaine treatment, respectively; P < 0.02) but not pyruvate-supported respiration (281 ± 12.5 and 267 ± 12.7 ngatomO min⁻¹ · mg⁻¹ · protein ± SEM; P = 0.45). Cocaine altered contractility, lusitropy, coronary resistance, and lactate production in isolated heart. These effects were each blunted in pioglitazone-treated hearts. The pioglitazone diet attenuated the drop in the rate-pressure product (P = 0.002), cocaine-induced diastolic dysfunction (P = 0.04), and myocardial vascular resistance (P = 0.05) compared with that of controls. Lactate production was higher in pretreated hearts (P = 0.008) and in ventricular myocytes cultured with pioglitazone (P = 0.0001). Cocaine inhibited octanoylcarnitine-supported mitochondrial respiration. A pioglitazone diet significantly attenuated the effects of cocaine on isolated heart. The authors postulate that inhibition of acylcarnitine exchange could contribute to cocaine-induced cardiac dysfunction and that metabolic modulation warrants additional study.

Appraisal predicts hemodynamic reactivity in a naturalistic stressor

Prior research has shown that appraisals are predictive of hemodynamic reaction patterns. The current study examined the relationship between appraisal and hemodynamic responding in a real-life stressful situation. Twenty-four men aged 19–28 wore a blood pressure monitor while presenting a paper in a class. Participant's appraisal self-reports were obtained prior to the stressor. Multilevel regression models were used to analyze the relationships between appraisal and myocardial responding (as measured by cardiac output) and vascular resistance (as measured by TPR). Pre-stressor appraisals were significantly associated with CO, both during the stressor ( Z = 2.03 p < .05) as well as during the 30-minute anticipation period preceding the stressor ( Z = 2.43 p < .01). In line with the predictions, relatively challenged participants showed higher CO. Pre-stressor appraisals significantly predicted TPR during anticipation ( Z = 2.70 p < .01) but these associations failed to reach significance during the stressor ( Z = 1.82, n.s.). As was predicted, during anticipation, increased threat was associated with increased TPR. Thus, during the anticipation period prior to the stressor, increased challenge was associated with decreased vascular resistance and increased myocardial reactivity. Further, increased threat was associated with increased vascular resistance and decreased myocardial reactivity. During the stressor increases in challenge were associated with further increases in myocardial responding but relationships between appraisal and vascular resistance were not significant. The current study shows that the relationship between appraisal and hemodynamic reactivity seen in laboratory studies are also present during naturally occurring stress. Our findings suggest that threat appraisals to naturalistic stressors contribute to an, arguably unhealthy, vascular reaction pattern.

Abstract 2016: Levosimendan Infusion in Patients with Myocardial Infarction and High Systemic Vascular Resistance

Background: Levosimendan, a novel inodilator, has been shown to improve hemodynamic function in patients with decompensated heart failure with preserved arterial blood pressure. Data on its use in patients with cardiogenic shock are scarce. The present series describes the 24-h hemodynamic effects of levosimendan as add-on therapy in patients with cardiogenic shock. Methods: Levosimendan was administered for 24 hours (dose ranging from 0.05 to 0.2μg/kg/min), in addition to catecholamines, in 25 patients who suffered from cardiogenic shock after acute myocardial infarction. Hemodynamic measurements were performed at baseline (prior to levosimendan infusion) and at 24 hours after initiation of levosimendan. Results: Hemodynamic improvement was evident only in patients (Group 1, n=13) with increased systematic vascular resistance (SVR&gt;18Wood). Levosimendan administration increased the cardiac index ( 2.1±0.4 l/min/m2 from 1.5±0.3l/min/m2, p=0.002) and cardiac power (0.645±0.179W from 0.462±0.164W, p=0.022) and decreased SVR (21±6.7Wood from 23±5Wood, p=0.001) and pulmonary cappillary wedge pressure (16±11mmHg from 23±5mmHg, p=0.059). On the other hand, patients with low systemic vascular resistance (SVR&lt;19Wood)) (Group B, n=12 ) did not have hemodynamic improvement with levosimendan administration. Conclusions: Levosimendan infusion added to catecholamines in patients with cardiogenic shock after myocardial infarction exerts hemodynamic benefit only in the subgroup of patients with high SVR.

Impact of Type 2 Diabetes on Nitric Oxide and Adrenergic Modulation of Myocardial Perfusion

Type 2 diabetic patients are characterized by a reduced adenosine-induced hyperemic myocardial perfusion, which may contribute to their increased cardiovascular morbidity. We hypothesized that the reduced hyperemia can be explained by functional changes in endothelial or autonomic nervous regulation. In 12 type 2 diabetic patients without signs of ischemic heart disease and 14 age-matched control subjects, myocardial perfusion was measured at rest, during adenosine, and during adenosine and alpha-receptor blockade (phentolamine) using positron emission tomography on two separate days: 1) with, and 2) without nitric oxide (NO) inhibition with N(G)-nitro-L-arginine methyl ester. Myocardial perfusion during adenosine was lower in type 2 diabetic patients compared with control subjects (P = 0.05). No significant effect of NO inhibition on myocardial perfusion during adenosine was found in any of the groups. In control subjects, alpha-receptor blockade increased hyperemic myocardial vascular resistance during NO inhibition, whereas no effect was observed in type 2 diabetic patients. At rest, a significant correlation was observed between rate-pressure product and myocardial perfusion in control subjects. NO inhibition and type 2 diabetes abolished this correlation. Endothelial and cardiac autonomic nerve function seems to play only a minimal role in the reduced hyperemic myocardial perfusion in type 2 diabetic patients. However, the linear correlation between resting perfusion and cardiac work appears to be abolished in type 2 diabetes and during NO synthase inhibition.

Ischaemic preconditioning causes increased myocardial vascular resistance but no myocardial contractility changes in pigs after OPCAB

The coronary vascular resistance (CVR) after off pump coronary bypass (OPCAB) surgery has never been clarified and ways of preventing stunning are wanted. We wished to investigate the effect of ischaemic preconditioning (IPC) on the CVR and stunning in the postoperative period after OPCAB. In 20 pigs (80 kg), 7 piezo-electric crystals were placed on the left ventricle to assess global and local myocardial contractility. Coronary vascular resistance was measured as the relation between perfusion pressure and coronary artery blood flow. IPC was obtained in ten pigs with one period of 10 min of coronary occlusion, followed by 15 min of reperfusion and 20 min of ischaemia. Ten control animals were exposed to 20 min of ischaemia only. Reperfusion was allowed for 120 min. The CVR was higher in the IPC group (measured by the slopes of the curves in the reperfusion period) (IPC: -0.33 (CI: (-0.62)-(-0.03)); 0.31 (CI: (-0.03)-(0.67)), P<0.005. There was no difference in the local myocardial contractility (slopes of the curves in the reperfusion period) (IPC: -0.004+/-0.01; -0.005+/-0.01). In conclusion, there was no alteration in myocardial contractility, but increased CVR in the early reperfusion period in animals preconditioned before sustained ischaemia.

Myocardial blood flow and coronary vascular resistance are dependent on thyroid function-a quantitative study using positron emission tomography and oxygen-15-labeled water

Myocardial blood flow and coronary vascular resistance are dependent on thyroid function-a quantitative study using positron emission tomography and oxygen-15-labeled water

1164-127 Whole body, myocardial, and coronary vascular insulin resistance in conscious dogs with pacing induced dilated cardiomyopathy

1164-127 Whole body, myocardial, and coronary vascular insulin resistance in conscious dogs with pacing induced dilated cardiomyopathy

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Microvasculature in acute myocardial ischemia: part I: evolving concepts in pathophysiology, diagnosis, and treatment.

Hypertension exacerbates the effect of hypercholesterolemia on the myocardial microvasculature.

Hypercholesterolemia (HC) and hypertension (HT) are both major risk factors for the development and progression of atherosclerotic heart disease, and their co-existence has been associated with an increased incidence of cardiac events in clinical studies. HC and HT are individually associated with abnormal myocardial vascular function, but whether HT exacerbates the HC-induced myocardial vascular dysfunction remains unclear. We studied in pigs the effect of renovascular HT superimposed on diet-induced HC (HC+HT) on myocardial perfusion and microvascular permeability in vivo (using electron-beam computed tomography) in response to cardiac challenge (i.v. adenosine and dobutamine). The involvement of systemic and myocardial tissue oxidative stress in vitro was assessed by oxidizability of LDL, levels of endogenous antioxidants, and tissue activities of radical-scavenger systems. While in normal animals myocardial perfusion increased in response to i.v. adenosine (+36+/-13%, P<0.05), in HC and HT alone the increase was blunted. In HC+HT myocardial perfusion response was further attenuated and significantly lower than normal, and myocardial vascular resistance failed to decrease (+7.6+/-8.8 vs. -21.0+/-5.8%, P=0.02 versus normal). HC+HT also showed blunted response to dobutamine, and augmented increases in microvascular permeability in vivo. These functional abnormalities were associated with increased systemic and myocardial tissue oxidative stress compared to HC or HT alone, and a synergistic decrease in endogenous antioxidant defenses in myocardial tissue. Furthermore, chronic antioxidant vitamin supplementation in combined HC and HT improved myocardial vascular responses. HT amplifies the HC-induced myocardial microvascular dysfunction in vivo and increased oxidative stress in vitro. These alterations may potentially play a role in the increased incidence of cardiac events observed when HC and HT co-exist.

Decrease in coronary blood flow reserve during hyperlipidemia is secondary to an increase in blood viscosity.

During maximal hyperemia, capillaries provide the greatest resistance to flow. A major determinant of capillary resistance is viscosity. We, therefore, hypothesized that abnormal coronary blood flow (CBF) reserve observed during hyperlipidemia is secondary to increased blood viscosity and not abnormal coronary vasomotion. Maximal hyperemia was induced in 9 dogs using adenosine. Serum triglyceride levels were increased by incremental doses of Intralipid. A good correlation was noted between serum triglyceride levels and blood viscosity (r=0.82). Neither total coronary blood volume nor myocardial blood volume changed with increasing serum triglyceride levels, indicating lack of vasomotion. Myocardial vascular resistance (MVR) increased with increasing triglyceride levels (r=0.84), while hyperemic myocardial blood flow (MBF) decreased (r=-0.64). The decrease in hyperemic MBF was associated with a decrease in blood velocity (r=-0.56). These findings were confirmed with direct intravital microscopic observations in the mice cremaster muscle. Increasing lipid levels in a fully dilated normal coronary bed causes no change in large or small vessel dimensions. Instead, the increase in blood viscosity causes capillary resistance to rise, which attenuates hyperemic CBF. Therefore, the abnormal CBF reserve associated with hyperlipidemia is due to increase blood viscosity and not abnormal vascular function.

Invited commentary

Invited commentary