Complete reversibility of physiological coronary vascular abnormalities in hypertrophied hearts produced by pressure overload in the rat.

Using an experimental model of ascending aortic banding in the rat, we examined whether coronary circulation abnormalities in hypertrophied hearts are reversible after debanding. 4-wk banding produced significant increases in in vivo left ventricular (LV) pressure (194 +/- 13 vs. 114 +/- 9 mmHg in shamoperated controls) and LV dry wt/body wt (48 +/- 5% above controls). In isolated hearts perfused with Krebs-Henseleit buffer, coronary flow rate (CFR) was estimated under nonworking conditions. During maximal vasodilation after 1 min-ischemia, CFR at a coronary perfusion pressure (CPP) of 100 mmHg and CFR/myocardidial mass at CPPs of 100 and 150 mmHg decreased significantly (72 +/- 5%; 53 +/- 4 and 61 +/- 4% of controls). 1 or 4 wk after debanding, LV systolic pressures were similar to control values, and the degree of myocardial hypertrophy decreased to levels 23 +/- 6 (P less than 0.01) and 11 +/- 6% (P less than 0.01) above their control values, respectively. At 1 wk there was no significant increase in CFR/myocardial mass, compared to values in the banded group (67 +/- 8 vs. 53 +/- 4% of controls at 100 mmHg and 67 +/- 9 vs. 61 +/- 4% at 150 mmHg of CPP). At 4 wk, CFR and the ratio had increased toward normal. Thus, decreased coronary perfusion in hypertrophied hearts is completely reversible.     

Hypoxic Hypoperfusion Fails to Induce Myocardial Hibernation in Anesthetized Swine

BACKGROUND: Congenital origin of the left coronary artery from the pulmonary artery (ALCAPA) results in chronically dysfunctional myocardium with the partial ability to recover after revascularization. We attempted to establish an ALCAPA syndrome in anesthetized pigs for 24 hours and to compare it with stunned and infarcted myocardium. METHODS AND RESULTS: In group 1 (n = 12), a bypass graft was interposed between the pulmonary artery and the left anterior descending coronary artery (LAD). Reduction of flow in the LAD with gradual increases in flow from the pulmonary artery resulted in an incremental reduction of segment shortening (8.9 +/- 5.3% at 24 hours vs 26.6 +/- 10% at baseline, P <.005). In group 3 (n = 5), 2 cycles of 10-minute LAD occlusion resulted in decreased segment shortening with slow recovery (at 24 hours 18.7 +/- 1.3% vs 24.2 +/- 4% at baseline, segment shortening with slow recovery (at 24 hours 18.7 +/- 1.3% vs 24.2 +/- 4% at baseline, P <.05). In group 3 (n = 6), 1-hour LAD occlusion reduced segment shortening at 24 hours to 4.7 +/- 5.2% (P <.005 vs baseline). Histological analysis of the LAD territory revealed severe degeneration, myolysis, and alteration of the chromatin structure in group 1 comparable to ischemic cell death in group 3, whereas control areas and the LAD area in group 2 showed only minor structural alterations. Infarct size/risk area, as measured by tetrazolium staining, was 49.8 +/- 11.2% in group 1, 9.3 +/- 8.1% in group 2 (P <.005), and 60.3 +/- 9% in group 3. CONCLUSION: Hypoxic myocardial hypoperfusion from the pulmonary artery results in myocardial necrosis in anesthetized pigs. These findings are in contrast to the concept of myocardial hibernation in the ALCAPA syndrome because in this model, hypoxic hypoperfusion failed to induce adaptation to preserve myocardial structure.     

Enalaprilat,losartan and LU 135252 in coronary blood flow regulation

BACKGROUND: High plasma levels of angiotensin II are found in several pathologies such as hypertension, heart failure and myocardial infarction. The effect of high concentrations of angiotensin II on coronary circulation is not well defined. The aim of the present study was to assess coronary blood flow regulation during tachycardia in the presence of elevated coronary plasma levels of angiotensin II, and the changes induced by ACE inhibition and blockade of angiotensin II and endothelin-A receptors. DESIGN: Left anterior coronary artery was catheterized in 38 pigs to infuse the study drugs. Saline was infused for 15 min. Then, the first atrial pacing was performed. The pigs were distributed to: Group 1 (n = 7) angiotensin II; Group 2 (n = 7) enalaprilat + angiotensin II; Group 3 (n = 9) the bradykinin B2 antagonist HOE 140 + enalaprilat + angiotensin II; Group 4 (n = 7) losartan + angiotensin II; and Group 5 (n = 8) endothelin-A receptor antagonist LU 135252 + angiotensin II. After giving these infusions, a second pacing was repeated. RESULTS: The increase in coronary blood flow induced by pacing with angiotensin II was reduced from 181 +/- 21% to 116 +/- 37% (P = 0.006 vs. saline). Enalaprilat, losartan and LU 135252 restored the capacity of coronary blood flow to increase during pacing (151 +/- 39%, 162 +/- 35% and 161 +/- 16%, respectively; P = NS, vs. saline), while HOE 140 abolished the effect of enalaprilat. CONCLUSIONS: Moderately elevated coronary concentrations of angiotensin II reduced coronary blood flow during pacing. Enalaprilat, losartan and LU 135252 restored the hyperaemic coronary flow to similar values observed with saline. The beneficial effect of ACE inhibition is mediated through an increase in bradykinin.     

Effects of vasopressin on left anterior descending coronary artery blood flow during extremely low cardiac output

Because of the possibility of vasopressin-mediated coronary vasospasm, this study was designed to assess effects of vasopressin compared to saline placebo on left anterior descending (LAD) coronary artery blood flow. Twelve anaesthetized domestic swine were prepared for LAD coronary artery blood flow measurement with ultrasonic flow probes, using cardiopulmonary by-pass adjusted to 10% of the prearrest cardiac output. This 10% value approximates that reported for cardiac output during conventional closed-chest CPR. After 4 min of untreated ventricular fibrillation, and 3 min of cardiopulmonary by-pass blood flow, 12 pigs were randomly assigned to receive intravenously, every 5 min, either vasopressin (0.4, 0.4, and 0.8 U/kg; n = 6) or saline placebo (n = 6). The mean +/- S.D. LAD coronary artery blood flow in the vasopressin and placebo pigs was comparable before cardiac arrest, and during cardiopulmonary by-pass low flow; but increased significantly (P < 0.05) 90 s after each of three vasopressin injections compared to placebo (78 +/- 1 versus 42 +/- 2 ml/min; 62 +/- 2 versus 36 +/- 1 ml/min; and 54 +/- 1 versus 27 +/- 1 ml/min), respectively. Coronary vascular resistance decreased significantly (P < 0.05 ) 90 s after each of three vasopressin and placebo injections. In this model, repeated bolus administration of vasopressin, given during simulated extremely low cardiac output improved LAD coronary artery blood flow to prearrest levels without affecting coronary vascular resistance. Conclusions: during extremely low blood flow using cardiopulmonary by-pass, vasopressin improves LAD coronary artery blood flow without affecting coronary vascular resistance.     

Reduction of Myocardial Necrosis After Glycosaminoglycan Administration: Effects of a Single Intravenous Administration of Heparin or N-Acetylheparin 2 Hours Before Regional Ischemia and Reperfusion

BACKGROUND: We determined if a single administration of heparin or nonanticoagulant N-acetylheparin could reduce myocardial injury resulting from a 90-minute occlusion of the left circumflex coronary artery (LCX) and 6 hours of reperfusion in the anesthetized canine. METHODS AND RESULTS: Heparin (2 mg/kg), N-acetylheparin (2 mg/kg), or vehicle, 0.9% sodium chloride (control), was administered intravenously to separate groups of animals 2 hours before LCX occlusion. To ensure parity of LCX ischemia, only animals with ischemic zone regional blood flow < 0.16 mL/min/g tissue were included in the final analysis. Hemodynamics did not differ among the three study groups. Infarct size as a percentage of the left ventricular area at risk was obtained for each group. Myocardial infarct size was 43.0 +/- 3.9% in the vehicle, 28.8 +/- 5.8% in the heparin (P <.05 vs vehicle) and 24.7 +/- 4.6% (P <.05 vs vehicle) in the N-acetylheparin-treated animals. CONCLUSIONS: Pretreatment with heparin or its nonanticoagulant derivative, N-acetylheparin, provides significant protection to the regionally ischemic and reperfused canine myocardium independent of either plasma glycosaminoglycan concentration or alterations in the coagulation system.     

Alpha 1-adrenoceptor activation mediates the infarct size-limiting effect of ischemic preconditioning through augmentation of 5'-nucleotidase activity.

We have reported that ischemic preconditioning may limit infarct size by increasing 5'-nucleotidase activity. The present study tested whether alpha 1-adrenoceptor stimulation in ischemic preconditioning mediates the infarct size-limiting effect through augmentation of 5'-nucleotidase activity. The coronary artery was occluded four times for 5 min separated by 5 min of reperfusion (ischemic preconditioning) in 82 dogs. Then the coronary artery was occluded for 90 min followed by 6 h of reperfusion. Infarct size normalized by risk area was smaller after ischemic preconditioning than in the control group (40.6 +/- 2.3 vs 6.7 +/- 2.0%, P < 0.001), even though no difference existed in endomyocardial collateral flow during ischemia (8.7 +/- 1.0 vs 8.9 +/- 1.0 ml/100 g per min). Ectosolic and cytosolic 5'-nucleotidase activity was increased after ischemic preconditioning. However, prazosin blunted the infarct size-limiting effect of ischemic preconditioning (infarct size: 42.8 +/- 3.7%). Intermittent alpha 1-adrenoceptor stimulation by methoxamine mimicked the increase in 5'-nucleotidase activity and the infarct size-limiting effect, which were abolished by alpha, beta,-methyleneadenosine 5'-diphosphate. Identical results were obtained in the conscious model (n = 20). Therefore, we conclude that increases in ectosolic 5'-nucleotidase activity due to alpha 1-adrenoceptor activation may contribute to the infarct size-limiting effect of ischemic preconditioning.     

The importance of ventricular septal morphology in the effectiveness of dual chamber pacing in hypertrophic obstructive cardiomyopathy

It has been reported that older patients with hypertrophic obstructive cardiomyopathy (HOCM) benefited the most from dual chamber (DDD) pacing. Since in older patients the distribution of septal hypertrophy and left ventricular (LV) cavity shape differs from that in younger patients, we decided to study the efficacy of DDD pacing on the reduction of LV outflow tract (LVOT) gradient in different patterns of septal hypertrophy. We compared HOCM patients with nonreversed septal curvature, thus preserving the elliptical LV cavity contour (common in the elderly), (group I) versus patients with reversed septal curvature, deforming the LV cavity to a crescent shape (common in the young), (group II). Eighteen HOCM patients were studied (11 patients in group I and 7 patients in group II). After implantation of a DDD pacemaker, the LVOT gradient was measured using Doppler echocardiography at various programmed AV delay intervals to determine the maximal percentage decrease of LVOT gradient from baseline. The measurement was repeated after at least a 6-month follow-up (chronic DDD pacing). The baseline LVOT gradient was comparable between groups (79 +/- 28 vs 81 +/- 25 mmHg, P = 0.92). The LVOT gradient reduction at acute DDD pacing was significantly greater in group I than group II (61 +/- 18% vs 23 +/- 10%, P = 0.0001). This difference in favor of the patients from group I was maintained at midterm follow-up (69 +/- 17% vs 40 +/- 17% P = 0.0076). In conclusion, patients with normal septal curvature and preserved elliptical LV cavity shape had a greater reduction of LVOT gradient after DDD pacing than patients with reversed septal curvature deforming LV cavity. The proposed criterion assessing the septal curvature may be useful to predict the efficacy of DDD pacing in the reduction of LVOT gradient.     

斑点追踪显像技术评价心肌扭转与心肌梗死范围相关性的实验研究

目的 应用斑点追踪显像技术评价急性心肌梗死(AMI)再灌注前、后左室心肌扭转,借以比较多个常规扭转指标与梗死范围的相关性,找出最能反映梗死范围的扭转指标.方法 小型猪15只,结扎左前降支120 min,分别检测结扎前、结扎后120 min、解除结扎后30 min、60 min、90 min、12 h各时间点常规超声指标以及扭转数据并进行比较.氯化硝基四氮唑蓝染色后计算心肌梗死范围.结果 AMI后心尖及左室各旋转/扭转角度指标均显著下降,再灌注12 h无明显改善.AMI即刻,左室整体扭转角度峰值及心尖整体旋转角度峰值与梗死范围的相关性明显优于同期其他扭转指标,相关系数分别为-0.81和-0.69(P均＜0.01);再灌注12 h相关性依然较好.结论 在AMI即刻及再灌注12 h内,左室整体扭转角度峰值及心尖整体旋转角度峰值是反映心肌梗死范围最敏感的扭转指标.

Abstract：

Objective To investigate the most sensitive markers of left ventricular(LV) torsion which can reflect infarct size by assessing the relationship between routine markers of LV torsion and infarct size using speckle tracking imaging (STI).Methods Fifteen open-chest pigs underwent 120 minutes of left anterior descending (LAD) ligation followed by 12 hours of reperfusion.Rotation and torsion of LV were obtained by STI before LAD occlusion,LAD occlusion immediately,and 30,60,90 minutes and 12 hours after reperfusion.Infarct size was measured by nitrotetrazolium blue chloride staining.Results LAD ligation resulted in a dramatic decrease in both subepicardial and subendocardial peak apical rotation or peak LV torsion.Twelve hours after reperfusion,all of the peak rotation and torsion remained significantly reduced (P ＜ 0.01 versus AMI).At AMI,peak bulk LV torsion and peak bulk apical rotation inversely correlated with infarct size (r = - 0.81,P ＜0.01; r = - 0.69,P ＜0.01).There existed the good relationship at 12-hour follow-up after reperfusion.The relationship was superior to that of other torsion markers.Conclusions Peak bulk LV torsion and peak bulk apical rotation are the most sensitive markers of LV torsion which can reflect infarct size.     

Pacing within the Ischemic Area Significantly Decreases the Left Ventricular Ejection Fraction during Experimental Acute Myocardial Infarction

Background: The aim of this study was to examine the effects on left ventricular (LV) function of LV apical or/and lateral wall pacing during an experimental acute myocardial infarction. Methods: In 12 anesthetized pigs, epicardial LV pacing at the apex or lateral wall, or at both sites simultaneously, was performed before and after left anterior descending (LAD) ligation. Data concerning LV function were obtained by two‐dimensional echo during spontaneous sinus rhythm (SR) and during pacing before and 15, 45, 60, and 90 minutes after LAD ligation. Results: Before ligation of the LAD, pacing at the lateral wall (48.04 ± 6.25%) or both sites (45.71 ± 6.31%) reduced the LV ejection fraction (EF) significantly (P < 0.01) in comparison to SR (55.44 ± 4.10%). However, during pacing at the apex (50.19 ± 6.50%), the reduction was not significant. After LAD ligation, the EF during lateral pacing (43.02 ± 7.71%) was significantly higher than during apical pacing (38.78 ± 8.26%, P < 0.04) but was not significantly different from that during dual‐site pacing (41.65 ± 8.69%). Conclusions: Pacing within the ischemic LV apical zone after LAD ligation impairs left ventricular ejection fraction, as compared with pacing the nonischemic LV lateral wall, and should therefore be avoided in clinical settings where the LV pacing site may be chosen. (PACE 2011; 63–71)     

Pertussis toxin-sensitive G proteins influence nitric oxide synthase III activity and protein levels in rat heart.

Inhibitory G protein activity (Gi) and nitric oxide (NO) modulate muscarinic-cholinergic (MC) inhibition of cardiac beta-adrenergic inotropic responses. We hypothesized that Gi mediates MC-NO synthase (NOS) signal transduction. Isoproterenol (0.2-0.8 microg/min) and acetylcholine (1 microM) were administered to isolated perfused rat hearts pretreated with saline (controls; n = 8) or pertussis toxin (PT; 30 microg/kg intraperitoneally 3 d before study; n = 20). PT abrogated in vitro ADP-ribosylation of Gi protein alpha subunit(s) indicating near-total decrease in Gi protein function. Isoproterenol increased peak +dP/dt in both control (peak isoproterenol effect: +2, 589+/-293 mmHg/s, P < 0.0001) and PT hearts (+3,879+/-474 mmHg/s, P < 0.0001). Acetylcholine reversed isoproterenol inotropy in controls (108+/-21% reduction of +dP/dt response, P = 0.001), but had no effect in PT hearts. In controls, NG-monomethyl-L-arginine (100 microM) reduced basal +dP/dt, augmented isoproterenol +dP/dt (peak effect: +4,634+/-690 mmHg/s, P < 0.0001), and reduced the MC inhibitory effect to 69+/-8% (P < 0.03 vs. baseline). L-arginine (100 M) had no effect in controls but in PT hearts decreased basal +dP/dt by 1, 426+/-456 mmHg/s (P < 0.005), downward-shifted the isoproterenol concentration-effect curve, and produced a small MC inhibitory effect (27+/-4% reduction, P < 0.05). This enhanced response to NO substrate was associated with increased NOS III protein abundance, and a three- to fivefold increase in in vitro calcium-dependent NOS activity. Neomycin (1 microM) inhibition of phospholipase C did not reverse L-arginine enhancement of MC inhibitory effects. These data support a primary role for Gi in MC receptor signal transduction with NOS in rat heart, and demonstrate regulatory linkage between Gi and NOS III protein levels.     

Mechanisms of optimized biventricular pacing in pulmonary stenosis: effects on left ventricular geometry in swine

We tested the hypothesis that optimized biventricular pacing (BiVP) enhances cardiac output (CO) during critical pulmonary stenosis (PS) by attenuating distortions in left ventricular (LV) geometry. Following median sternotomy in six anesthetized pigs, heart block was induced by ethanol ablation. During epicardial, DDD BiVP, atrioventricular delay (AVD) was varied from 60 ms to 180 ms in 30 ms increments. At the AVD with the highest CO right-left delay (RLD) was varied from (+) 80 ms (RV first) to (-) 80 ms (LV first) in 20 ms increments. At each pacing setting, aortic flow, ECG, and LV diameter were measured in the control state (CON) and during PS, created by snaring the pulmonary artery until CO decreased 50%. Short axis LV echocardiograms were obtained at (+) and (-) 80 ms. In CON, RLD had no effect on function or geometry. During PS optimum BiVP resulted in significant increases in CO (1.12 L/min +/- 0.13 SEM at RLD =+ 40 ms versus 0.92 +/- 0.12 at RLD = 0 and 0.73 +/- 0.08 at RLD =-80), and LV fractional shortening (8.97%+/- 0.51% at RLD =+ 40 ms versus 7.34%+/- 0.58% at RLD = 0 and 6.21%+/- 0.66% at RLD =-80). In addition, LV eccentricity with (-) RLD was significantly different versus CON at both end-diastole (0.79 +/- 0.07 vs 1.02 +/- 0.03, P = 0.011 Student's t-test) and end-systole (0.83 +/- 0.05 vs 1.00 +/- 0.02, P = 0.017). However, with (+) RLD differences versus CON were not significant at either end-diastole (0.88 +/- 0.06 vs 0.99 +/- 0.03) or end-systole (0.92 +/- 0.03 vs 1.01 +/- 0.03). In swine hearts with PS, optimized BiVP increases CO, fractional shortening, and LV symmetry. BiVP warrants further study as treatment for acute postoperative heart failure.     

Effect of right ventricular apex pacing on the Tei index and brain natriuretic peptide in patients with a dual-chamber pacemaker

BACKGROUND: Asynchronous electrical activation induced by right ventricular apex (RVA) pacing can cause various abnormalities in left ventricular (LV) function, particularly in the context of severe LV dysfunction or structural heart disease. However, the effect of RVA pacing in patients with normal LV and right ventricular (RV) function has not been fully elucidated. The aim of this study was to characterize the effects of RVA pacing on LV and RV function by assessing isovolumic contraction time and isovolumic relaxation time divided by ejection time (Tei index) and by assessing changes in plasma brain natriuretic peptide (BNP). METHODS: Doppler echocardiographic study and BNP measurements were performed at follow-up (mean intervals from pacemaker implantation, 44+/-75 months) in 76 patients with dual chamber pacemakers (sick sinus syndrome, n=30; atrioventricular block, n=46) without structural heart disease. Patients were classified based on frequency of RVA pacing, as determined by 24-hour ambulatory electrocardiogram (ECG) that was recorded just before echocardiographic study: pacing group, n=46 patients with RVA pacing>or=50% of the time, percentage of ventricular paced 100+/-2%; sensing group, n=30, patients with RVA pacing<50% of the time, percentage of ventricular paced 3+/-6%. RESULTS: There was no significant difference in mean heart rate derived from 24-hour ambulatory ECG recordings when comparing the two groups (66+/-11 bpm vs 69+/-8 bpm). LV Tei index was significantly higher in pacing group than in sensing group (0.67+/-0.17 vs 0.45+/-0.09, P<0.0001), and the RV Tei index was significantly higher in pacing group than in sensing group (0.34+/-0.19 vs 0.25+/-0.09, P=0.011). Furthermore, BNP levels were significantly higher in pacing group than in sensing group (40+/-47 pg/mL vs 18+/-11 pg/mL, P=0.017). With the exception of LV diastolic dimension (49+/-5 mm vs 45+/-5 mm, P=0.012), there were no significant differences in other echocardiographic parameters, including left atrium (LA) diameter (35+/-8 mm vs 34+/-5 mm), LA volume (51+/-27 cm3 vs 40+/-21 cm3), LV systolic dimension (30+/-6 mm vs 29+/-7 mm), or ejection fraction (66+/-9% vs 63+/-11%), when comparing the two groups. CONCLUSIONS: These findings suggest that the increase of LV and RV Tei index, LVDd, and BNP are highly correlated with the frequency of the RVA pacing in patients with dual chamber pacemakers.     

Echocardiographic evaluation of ventricular remodeling in a mouse model of myocardial infarction.

Gene-targeting in mice is a powerful tool to define molecular mechanisms of ischemic heart disease that determine infarct size, postinfarct left ventricular (LV) remodeling, and arrhythmogenesis. Coronary ligation in mice is becoming a widely used model of myocardial infarction (MI), but the pathophysiologic consequences of MI in mice and its relevance to human MI have not been fully elucidated. To characterize structural and functional changes during evolving MI, we analyzed 2-dimensional-based reconstruction of the left ventricle by noninvasive echocardiography obtained 1 day and 1 week after surgical ligation of the left anterior descending coronary artery in mice. Sequential 2-dimensional short-axis cineloops of the left ventricle were used to measure LV mass, and LV volumes at end-diastole and end-systole. Echocardiographic infarct size was estimated by measuring the volume of akinetic LV segments. Histologic infarct size was measured by planimetry of 9 transverse sections of each heart. There was close correlation between the 2 methods (31% +/- 20% of LV mass and 34% +/- 17% of LV area, respectively; y =.83x + 7.9, r = 0.96, P <.01). LV volumes at end diastole increased significantly between 1 day and 1 week (51 +/- 17 microL vs 78 +/- 46 microL, respectively, P <.05). The relative change in LV volumes at end diastole varied as a function of infarct size (r = 0.93, P <.01). LV mass and the extent of hypertrophy of noninfarcted segments also varied with infarct size (r = 0.92, P <.01; r = 0.90, P <.01, respectively). Thus, echocardiography is an accurate noninvasive tool for determination of infarct size and quantitative characterization of postinfarct remodeling in the mouse model of MI. Alterations in cardiac structure and function after coronary ligation in mice closely resemble pathophysiologic changes in human ischemic heart disease.     

Effect of diltiazem on infarct size, reperfusion flow and flow reserve: the effect of timing of treatment

This study was performed to determine if improved subendocardial reflow seen with diltiazem pretreatment after left circumflex coronary (LCX) occlusion is due to a direct vasodilatory effect of diltiazem on the reperfused bed or due to an increased flow maximum or reserve. In the first part of this study anesthetized dogs were subjected to saline or diltiazem (infused starting before, 10 min after LCX occlusion or 2 min before reperfusion; 0.18 mg/kg + 0.45 mg/kg/hr i.v. for all groups) treatment with a 90-min LCX occlusion and 5-hr reperfusion and myocardial blood flow and infarct size were determined at the end of the experiment. In the second part, maximal flow using intracoronary adenosine was determined at 1 and 3 hr postreperfusion in the ischemic bed when pretreated with saline or diltiazem. Myocardial infarct size was reduced significantly only in animals pretreated with diltiazem compared to saline-treated animals. At 1-hr postreperfusion, subendocardial flow (microspheres) was significantly higher only with diltiazem pretreatment compared to the saline group (100 +/- 17 vs. 54 +/- 8 ml/min/100 g, respectively) and subendocardial reperfusion flows were negatively correlated to infarct size (r = 0.97, P less than .05). Thus, diltiazem only improves reflow and infarct size when infused before occlusion and this improved reflow does not occur via a direct vasodilator action of diltiazem. When maximal vasodilating doses of adenosine were given, flow in the ischemic region was nearly identical for saline and diltiazem pretreated groups despite higher preadenosine flows in the diltiazem group (higher resting flow occurred at the expense of the existing flow reserve).(ABSTRACT TRUNCATED AT 250 WORDS)     

Thrombosis in one coronary artery causes generalized coronary vasoconstriction in a dog model of unstable angina

We investigated the effect of thrombosis in one coronary artery upon the vascular resistance of another coronary artery. In previous investigations, using an animal model of unstable angina, we have observed increased resistance downstream from thrombus within a left circumflex coronary artery (LCx) stenosis and vasoconstriction of collateral vessels from the left anterior descending artery (LAD) supplying the distal LCx vascular bed. In the present paper, we induced thrombosis within a stenosis of the LCx of 16 beagle dogs, and observed the changes in blood flow to the myocardium supplied by the LAD using the radioactive microsphere technique. This blood flow decreased with thrombosis (P = 0.005) in these animals, whereas it did not do so in three time-control experiments. The pressures across the coronary vascular bed, i.e. arterial pressure to coronary venous pressure (coronary sinus catheter), did not change. Thus the vascular resistance of the LAD bed increased significantly from 147 +/- ll.5 mmHg/ml/sec/g of tissue to 172 +/- 13.4 mmHg/ml/sec/g of tissue (P = 0.02). As the LAD territory is not perfused with blood from the artery containing thrombus, we conclude that the effect observed is caused either by release of vasoconstrictors from the thrombus into the general circulation, or by activation of a neural reflex vasoconstriction. The study suggests that unstable angina involving thrombosis in one coronary artery is a global coronary vascular disease.     

A Comparison of Ventricular Function During High Right Ventricular Septal and Apical Pacing after His-Bundle Ablation for Refractory Atrial Fibrillation

This study compares LV performance during high right ventricular septal (RVS) and apical (RVA) pacing in patients with LV dysfunction who underwent His-bundle ablation for chronic AF. We inserted a passive fixation pacing electrode into the RVA and an active fixation electrode in the RVS. A dual chamber, rate responsive pulse generator stimulated the RVA through the ventricular port and the RVS via the atrial port. Patients were randomized to initial RVA (VVIR) or RVS (AAIR) pacing for 2 months. The pacing site was reversed during the next 2 months. At the 2 and 4 month follow-up visit, each patient underwent a transthoracic echocardiographical study and a rest/exercise first pass radionuclide ventriculogram. We studied nine men and three women (mean age of 68 +/- 7 years) with congestive heart failure functional Class (NYHA Classification): I (3 patients), II (7 patients), and III (2 patients). The QRS duration was shorter during RVS stimulation (158 +/- 10 vs 170 +/- 11 ms, P < 0.001). Chronic capture threshold and lead impedance did not significantly differ. LV fractional shortening improved during RVS pacing (0.31 +/- 0.05 vs 0.26 +/- 0.07, P < 0.01). RVS activation increased the resting first pass LV ejection fraction (0.51 +/- 0.14 vs 0.43 +/- 0.10, P < 0.01). No significant difference was observed during RVS and RVA pacing in the exercise time (5.6 +/- 3.2 vs 5.4 +/- 3.1, P = 0.6) or the exercise first pass LV ejection fraction (0.58 +/- 0.15 vs 0.55 +/- 0.16, P = 0.2). The relative changes in QRS duration and LV ejection fraction at both pacing sites showed a significant correlation (P < 0.01). We conclude that RVS pacing produces shorter QRS duration and better chronic LV function than RVA pacing in patients with mild to moderate LV dysfunction and chronic AF after His-bundle ablation.     

Insulin action on heart and skeletal muscle glucose uptake in essential hypertension.

Essential hypertension is characterized by skeletal muscle insulin resistance but it is unknown whether insulin resistance also affects heart glucose uptake. We quantitated whole body (euglycemic insulin clamp) and heart and skeletal muscle (positron emission tomography and 18F-fluoro-2-deoxy-D-glucose) glucose uptake rates in 10 mild essential hypertensive (age 33 +/- 1 yr, body mass index 23.7 +/- 0.8 kg/m2, blood pressure 146 +/- 3/97 +/- 3 mmHg, VO2max 37 +/- 3 ml/kg per min) and 14 normal subjects (29 +/- 2 yr, 22.5 +/- 0.5 kg/m2, 118 +/- 4/69 +/- 3 mmHg, 43 +/- 2 ml/kg per min). Left ventricular mass was similar in the hypertensive (155 +/- 15 g) and the normotensive (164 +/- 13 g) subjects. In the hypertensives, both whole body (28 +/- 3 vs 44 +/- 3 mumol/kg per min, P < 0.01) and femoral (64 +/- 11 vs 94 +/- 8 mumol/kg muscle per min, P < 0.05) glucose uptake rates were decreased compared to the controls. In contrast, heart glucose uptake was 33% increased in the hypertensives (939 +/- 51 vs 707 +/- 46 mumol/kg muscle per min, P < 0.005), and correlated with systolic blood pressure (r = 0.66, P < 0.001) and the minute work index (r = 0.48, P < 0.05). We conclude that insulin-stimulated glucose uptake is decreased in skeletal muscle but increased in proportion to cardiac work in essential hypertension. The increase in heart glucose uptake in mild essential hypertensives with a normal left ventricular mass may reflect increased oxygen consumption and represent an early signal which precedes the development of left ventricular hypertrophy.     

Blood flow in the left anterior descending coronary artery in children with ventricular septal defect.

High-frequency echocardiography offers a noninvasive approach for imaging left anterior descending coronary artery (LAD) blood flow from a transthoracic window. The purpose of this study was to assess the effects of left ventricular (LV) volume overload on LAD flow in pediatric patients with ventricular septal defect (VSD). The study subjects consisted of 38 children with VSD and 15 healthy children. LV mass, LAD diameter, and LAD flow were measured by using transthoracic echocardiography, then LAD diameter and LV mass were indexed for body surface area. Pulmonary to systemic flow ratios (Qp/Qs) were obtained by cardiac catheterization. The Qp/Qs ratios ranged from 1.2 to 3.1 (mean 2.1 +/- 0.5). The mean LAD flow velocities, flow velocity integrals, and flow volumes were significantly higher in the patients than in the control subjects. LAD flow velocity and flow volume showed significant positive correlations with Qp/Qs, LV mass, and LV end-diastolic volume. Stepwise regression analysis revealed that Qp/Qs was the most important determinant of both LAD flow velocity (r(2) = 0.45, P < .0001) and LAD flow volume (r(2) = 0.44, P < .0001). The ratios of LAD flow volume to LV mass did not differ between the 2 groups. In 8 patients who underwent surgical treatment, LAD flow velocity, flow velocity integral, and flow volume decreased significantly after surgery. The current results suggest that patients with VSD have a higher resting coronary blood flow, and that LAD flow pattern is dependent on LV volume overload and changes after surgery.     

Does RV Lead Positioning Provide Additional Benefit to Cardiac Resynchronization Therapy in Patients with Advanced Heart Failure?

BACKGROUND AND OBJECTIVES: The left ventricular (LV) stimulation site is currently recommended to position the lead at the lateral wall. However, little is known as to whether right ventricular (RV) lead positioning is also important for cardiac resynchronization therapy. This study compared the acute hemodynamic response to biventricular pacing (BiV) at two different RV stimulation sites: RV high septum (RVHS) and RV apex (RVA). METHODS AND RESULTS: Using micro-manometer-tipped catheter, LV pressure was measured during BiV pacing at RV (RVA or RVHS) and LV free wall in 33 patients. Changes in LV dP/dt(max) and dP/dt(min) from baseline were compared between RVA and RVHS. BiV pacing increased dP/dt(max) by 30.3 +/- 1.2% in RVHS and by 33.3 +/- 1.7% in RVA (P = n.s.), and decreased dP/dt(min) by 11.4 +/- 0.7% in RVHS and by 13.0 +/- 1.0% in RVA (P = n.s.). To explore the optimal combination of RV and LV stimulation sites, we assessed separately the role of RV positioning with LV pacing at anterolateral (AL), lateral (LAT), or posterolateral (PL) segment. When the LV was paced at AL or LAT, the increase in dP/dt(max) with RVHS pacing was smaller than that with RVA pacing (AL: 12.2 +/- 2.2% vs 19.3 +/- 2.1%, P < 0.05; LAT: 22.0 +/- 2.7% vs 28.5 +/- 2.2%, P < 0.05). There was no difference in dP/dt(min) between RVHS- and RVA pacing in individual LV segments. CONCLUSIONS: RVHS stimulation has no overall advantage as an alternative stimulation site for RVA during BiV pacing. RVHS was equivalent with RVA in combination with the PL LV site, while RVA was superior to RVHS in combination with AL or LAT LV site.     

Assessment of coronary flow reserve with transthoracic Doppler echocardiography: comparison among adenosine, standard-dose dipyridamole, and high-dose dipyridamole.

Coronary flow reserve (CFR), defined as a ratio of hyperemic-to-basal coronary flow velocity, provides important information about the functional aspect of coronary circulation. However, it usually is determined by invasive methods during catheterization. Recent studies have shown that transthoracic Doppler echocardiography (TTDE) may be useful in the measurement of coronary flow velocity in the distal portion of the left anterior descending coronary artery (LAD). The vasodilators used for hyperemia are adenosine and dipyridamole. However, the coronary vasodilative response and systemic hemodynamic effects of the two agents have not been directly compared with TTDE. We assessed blood flow velocity and vascular resistance in the distal LAD by TTDE during an intravenous 2-minute adenosine infusion (140 microg/kg/min) and low- (0.56 mg/kg) and high-dose dipyridamole (0. 84 mg/kg) infusion in 25 patients with patent LAD. Coronary flow velocity was successfully recorded in 20 patients (80%) during baseline and the consecutive vasodilator-infusion period. Compared with low-dose dipyridamole, adenosine infusion induced a higher CFR (3.7 +/- 0.87 vs 2.73 +/- 0.65; P <.05) and a lower coronary resistance index (0.31 +/- 0.04 vs 0.35 +/- 0.08; P <.05). But by increasing the dipyridamole dose to 0.84 mg/kg, the values of the CFR and coronary resistance index became comparable to those of adenosine infusion (2.85 +/- 0.78 vs 3.03 +/- 0.7, P = not significant [NS]; 0.33 +/- 0.04 vs 0.32 +/- 0.09, P = NS; respectively). We conclude that adenosine seems to be a favorable vasodilator for the measurement of CFR with TTDE.