Alternative Approaches to the Assessment of the Systemic Circulation and Left Ventricular Performance: A Proof-of-Concept Study.

BACKGROUND: The purpose of this article is to examine the systemic circulation and left ventricular (LV) performance by alternative, nonconventional approaches: systemic vascular conductance (G SV ) and the head-capacity relation (ie, the relation between LV pressure and cardiac output), respectively; in so doing, we aspired to present a novel and improved interpretation of integrated cardiovascular function. METHODS: In 16 open-chest, anaesthetized pigs, we measured LV pressure (P LV ), central aortic pressure (P Ao ), and central venous pressure (P CV ) and aortic flow (Q Ao ). We calculated heart rate (HR), stroke volume, cardiac index (CI = cardiac output/body weight), mean PLV ( P ¯ LV ) , and the average arteriovenous pressure difference ( Δ P = P ¯ Ao - P ¯ CV ); G SV  = CI/( P ¯ Ao - P ¯ CV ). We studied the effects of changing loading conditions with the administration of phenylephrine (Δ P ¯ Ao ≥ +25 mm Hg), isoproterenol (ΔHR ∼+25%), sodium nitroprusside (Δ P ¯ Ao ≥ -25 mm Hg), and proximal aortic constriction (to maximize developed P LV and minimize Q Ao ). RESULTS: Sodium nitroprusside and isoproterenol increased G SV compared with phenylephrine and constriction. A maximum head-capacity curve was derived from pooled data using nonlinear regression on the maximum P ¯ LV values in Q Ao bins 12.5 mL/min/kg wide. The head-capacity relation and the plots of conductance were combined using CI as a common axis, which illustrated that CI is the output of the heart and the input of the circulation. CONCLUSIONS: Thus, at a given CI, G SV determines the driving pressure and, thereby, P Ao . We also demonstrated how decreases in G SV compensate for arterial hypotension by restoring the arteriovenous pressure difference and arterial pressure.

CONTEXTE: Le présent article examine l'efficacité de la circulation générale et la fonction ventriculaire gauche à l'aide de paramètres de rechange non conventionnels, soit la conductance vasculaire systémique (G VS ) pour l'une et la relation pression-volume (c.-à-d. la relation entre la pression ventriculaire gauche et le débit cardiaque) pour l'autre, dans le but de présenter une interprétation nouvelle et améliorée de la fonction cardiovasculaire intégrée. MÉTHODOLOGIE: Chez 16 porcs anesthésiés, nous avons mesuré à thorax ouvert la pression ventriculaire gauche (P VG ), la pression aortique centrale (P AC ), la pression veineuse centrale (P VC ) et le flux aortique (Q A ). Nous avons établi la fréquence cardiaque (FC), le volume d'éjection systolique, l'index cardiaque (IC; rapport entre le débit cardiaque et le poids corporel), la P VG moyenne ( P ¯ VG ) et la différence de pression artérioveineuse moyenne ( Δ P = P ¯ A C − P ¯ V C ); G VS  = IC/( P ¯ AC − P ¯ VC ). Nous avons aussi étudié les effets d'une modification des conditions de charge cardiaque provoquée par l'administration de phényléphrine (Δ P ¯ AC ≥ + 25 mmHg), d'isoprotérénol (ΔFC d'environ + 25 %) ou de nitroprussiate de sodium (Δ P ¯ AC ≥ − 25 mmHg) et par la constriction de l'aorte proximale (pour maximiser la P VG développée et réduire le plus possible le Q A ). RÉSULTATS: Le nitroprussiate de sodium et l'isoprotérénol ont augmenté la G VS comparativement à la phényléphrine et à la constriction. Une courbe de la relation pression-volume maximale a été dérivée à partir des données groupées, au moyen d'une régression non linéaire sur les valeurs maximales de la P ¯ VG réparties dans des classes de Q A de 12,5 ml/min/kg d'amplitude. La courbe de la relation pression-volume et le tracé de la conductance ont été superposés en utilisant l'IC comme axe commun, ce qui a permis de constater que l'IC correspond au débit cardiaque et au volume entrant dans la circulation. CONCLUSIONS: Pour un IC donné, la G VS détermine la pression motrice et donc, la P AC . Nous avons aussi démontré comment une diminution de la G VS compense l'hypotension artérielle en rétablissant la différence de pression artérioveineuse et la pression artérielle.

Comparison of Cardiac Magnetic Resonance Imaging and Echocardiography in Assessment of Left Ventricular Hypertrophy in Fabry Disease.

BACKGROUND: Cardiac hypertrophy in Fabry disease can be assessed using the left ventricular mass index (LVMI) with either echocardiography (LVMI-ECHO) or magnetic resonance imaging (LVMI-CMR). METHODS: A retrospective case series of patients with Fabry disease in Alberta involved a cross-sectional analysis of 32 patients and a longitudinal analysis of 14 of these patients with at least 4 serial CMR measurements. RESULTS: The cross-sectional analysis showed the mean LVMI-ECHO was 97.8 ± 26.0 g/m2, which was higher compared with LVMI-CMR at 81.1 ± 26.9 g/m2 with a mean bias of 16.7 g/m2 (P < 0.001). In the longitudinal analysis, LVMI-ECHO was higher, with an estimated marginal mean of 96.21 ± 6.13 (mean ± standard error of the mean [SEM]) compared with 71.18 ± 5.99 for LVMI-CMR (P < 0.01; generalized estimating equations). There was an association between an increase in LVMI-CMR over time with the presence of cardiac fibrosis, and patients treated with enzyme replacement therapy (ERT) had slower increases than those without therapy. LVMI-ECHO failed to detect these associations owing to the higher variability and tendency to overestimate the LVMI. CONCLUSIONS: We propose the preferred method for measuring LVMI is CMR in patients with Fabry disease.

A prospective evaluation of the established criteria for heart failure with preserved ejection fraction using the Alberta HEART cohort.

AIMS: Heart failure with a preserved ejection fraction (HF-PEF) remains a difficult clinical diagnosis. The aim of this study was to test the utility of established criteria to classify patients with HF-PEF. We prospectively enrolled patients into one of five groups across a spectrum of cardiac disease and applied three different criteria for HF-PEF and calculated diagnostic metrics. METHODS AND RESULTS: A total of 565 patients were included in the analysis, including 170 patients with an adjudicated diagnosis of HF-PEF, 152 patients with heart failure with reduced ejection fraction, 152 patients at risk for heart failure, and 91 age-matched healthy controls. For the diagnosis of HF-PEF, the positive likelihood ratios were 6.1, 6.9, and 4.8 for the Zile, European Society of Cardiology (ESC) 2007, and ESC 2016 criteria, respectively. The negative likelihood ratios were 0.58, 0.60, and 0.42 for the Zile, ESC 2007, and ESC 2016 criteria, respectively. All three criteria lacked sensitivity to detect HF-PEF (46.5%, 44.1%, and 51.8%, respectively) but were highly specific (92.4%, 93.9%, and 89%, respectively). We further evaluated the criteria to distinguish HF-PEF from other diagnoses after excluding heart failure with reduced ejection fraction; the results were similar. CONCLUSIONS: In this community based cohort, the likelihood ratios of the existing criteria for HF-PEF were not at the level necessary to be considered diagnostic. Improved criteria for the diagnosis of patients with HF-PEF are needed.

The reservoir-wave approach to characterize pulmonary vascular-right ventricular interactions in humans.

Using the reservoir-wave approach (RWA) we previously characterized pulmonary vasculature mechanics in a normal canine model. We found reflected backward-traveling waves that decrease pressure and increase flow in the proximal pulmonary artery (PA). These waves decrease right ventricular (RV) afterload and facilitate RV ejection. With pathological alterations to the pulmonary vasculature, these waves may change and impact RV performance. Our objective in this study was to characterize PA wave reflection and the alterations in RV performance in cardiac patients, using the RWA. PA pressure, Doppler-flow velocity, and pulmonary arterial wedge pressure were measured in 11 patients with exertional dyspnea. The RWA was employed to analyze PA pressure and flow; wave intensity analysis characterized PA waves. Wave-related pressure was partitioned into two components: pressures due to forward-traveling and to backward-traveling waves. RV performance was assessed by examining the work done in raising reservoir pressure and that associated with the wave components of systolic PA pressure. Wave-related work, the mostly nonrecoverable energy expended by the RV to eject blood, tended to vary directly with mean PA pressure. Where PA pressures were lower, there were pressure-decreasing/flow-increasing backward waves that aided RV ejection. Where PA pressures were higher, there were pressure-increasing/flow-decreasing backward waves that impeded RV ejection. Pressure-increasing/flow-decreasing backward waves were responsible for systolic notches in the Doppler flow velocity profiles in patients with the highest PA pressure. Pulmonary hypertension is characterized by reflected waves that impede RV ejection and an increase in wave-related work. The RWA may facilitate the development of therapeutic strategies.

A pharmacologic activator of endothelial KCa channels increases systemic conductance and reduces arterial pressure in an anesthetized pig model.

SKA-31, an activator of endothelial KCa2.3 and KCa3.1 channels, reduces systemic blood pressure in mice and dogs, however, its effects in larger mammals are not well known. We therefore examined the hemodynamic effects of SKA-31, along with sodium nitroprusside (SNP), in anesthetized, juvenile male domestic pigs. Experimentally, continuous measurements of left ventricular (LV), aortic and inferior vena cava (IVC) pressures, along with flows in the ascending aorta, carotid artery, left anterior descending coronary artery and renal artery, were performed during acute administration of SKA-31 (0.1, 0.3, 1.0, 3.0 and 5.0mg/ml/kg) and a single dose of SNP (5.0 µg/ml/kg). SKA-31 dose-dependently reduced mean aortic pressure (mPAO), with the highest dose decreasing mPAO to a similar extent as SNP (-23 ± 3 and -28 ± 4 mmHg, respectively). IVC pressure did not change. Systemic conductance and conductance in coronary and carotid arteries increased in response to SKA-31 and SNP, but renal artery conductance was unaffected. There was no change in either LV stroke volume (SV) or heart rate (versus the preceding control) for any infusion. With no change in SV, drug-evoked decreases in LV stroke work (SW) were attributed to reductions in mPAO (SW vs. mPAO, r(2)=0.82, P<0.001). In summary, SKA-31 dose-dependently reduced mPAO by increasing systemic and arterial conductances. Primary reductions in mPAO by SKA-31 largely account for associated decreases in SW, implying that SKA-31 does not directly impair cardiac contractility.

The Alberta Heart Failure Etiology and Analysis Research Team (HEART) study.

BACKGROUND: Nationally, symptomatic heart failure affects 1.5-2% of Canadians, incurs $3 billion in hospital costs annually and the global burden is expected to double in the next 1-2 decades. The current one-year mortality rate after diagnosis of heart failure remains high at >25%. Consequently, new therapeutic strategies need to be developed for this debilitating condition. METHODS/DESIGN: The objective of the Alberta HEART program (http://albertaheartresearch.ca) is to develop novel diagnostic, therapeutic and prognostic approaches to patients with heart failure with preserved ejection fraction. We hypothesize that novel imaging techniques and biomarkers will aid in describing heart failure with preserved ejection fraction. Furthermore, the development of new diagnostic criteria will allow us to: 1) better define risk factors associated with heart failure with preserved ejection fraction; 2) elucidate clinical, cellular and molecular mechanisms involved with the development and progression of heart failure with preserved ejection fraction; 3) design and test new therapeutic strategies for patients with heart failure with preserved ejection fraction. Additionally, Alberta HEART provides training and education for enhancing translational medicine, knowledge translation and clinical practice in heart failure. This is a prospective observational cohort study of patients with, or at risk for, heart failure. Patients will have sequential testing including quality of life and clinical outcomes over 12 months. After that time, study participants will be passively followed via linkage to external administrative databases. Clinical outcomes of interest include death, hospitalization, emergency department visits, physician resource use and/or heart transplant. Patients will be followed for a total of 5 years. DISCUSSION: Alberta HEART has the primary objective to define new diagnostic criteria for patients with heart failure with preserved ejection fraction. New criteria will allow for targeted therapies, diagnostic tests and further understanding of the patients, both at-risk for and with heart failure. TRIAL REGISTRATION: ClinicalTrials.gov NCT02052804.

Genesis of the characteristic pulmonary venous pressure waveform as described by the reservoir-wave model.

Conventional haemodynamic analysis of pulmonary venous and left atrial (LA) pressure waveforms yields substantial forward and backward waves throughout the cardiac cycle; the reservoir wave model provides an alternative analysis with minimal waves during diastole. Pressure and flow in a single pulmonary vein (PV) and the main pulmonary artery (PA) were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading, and positive-end expiratory pressure (PEEP) were observed. The reservoir wave model was used to determine the reservoir contribution to PV pressure and flow. Subtracting reservoir pressure and flow resulted in 'excess' quantities which were treated as wave-related.Wave intensity analysis of excess pressure and flow quantified the contributions of waves originating upstream (from the PA) and downstream (from the LA and/or left ventricle (LV)).Major features of the characteristic PV waveform are caused by sequential LA and LV contraction and relaxation creating backward compression (i.e.pressure-increasing) waves followed by decompression (i.e. pressure-decreasing) waves. Mitral valve opening is linked to a backwards decompression wave (i.e. diastolic suction). During late systole and early diastole, forward waves originating in the PA are significant. These waves were attenuated less with volume loading and delayed with PEEP. The reservoir wave model shows that the forward and backward waves are negligible during LV diastasis and that the changes in pressure and flow can be accounted for by the discharge of upstream reservoirs. In sharp contrast, conventional analysis posits forward and backward waves such that much of the energy of the forward wave is opposed by the backward wave.

Systemic vascular effects of acute electrical baroreflex stimulation.

We intended to determine if acute baroreflex activation therapy (BAT) increases venous capacitance and aortic conductance. BAT is effective in resistant hypertension, but its effect on the systemic vasculature is poorly understood. Left ventricular (LV) and aortic pressures and subdiaphragmatic aortic and caval flows (ultrasonic) were measured in six anesthetized dogs. Changes in abdominal blood volume (Vabdominal) were estimated as the integrated difference in abdominal aortic inflow and caval outflow. An electrode was implanted on the right carotid sinus. Data were measured during control and BAT. Next, sodium nitroprusside (SNP) was infused and BAT was subsequently added. Finally, angiotensin II (ANG II) was infused, and three increased BAT currents were added. We found that BAT decreased mean aortic pressure (PAo) by 22.5 ± 1.3 mmHg (P < 0.001) and increased aortic conductance by 16.2 ± 4.9% (P < 0.01) and Vabdominal at a rate of 2.2 ± 0.6 ml·kg(-1)·min(-1) (P < 0.01). SNP decreased PAo by 17.4 ± 0.7 mmHg (P < 0.001) and increased Vabdominal at a rate of 2.2 ± 0.7 ml·kg(-1)·min(-1) (P < 0.05). During the SNP infusion, BAT decreased PAo further, by 26.0 ± 2.1 mmHg (P < 0.001). ANG II increased PAo by 40.4 ± 3.5 mmHg (P = 0.001). When an increased BAT current was added, PAo decreased to baseline (P < 0.01) while aortic conductance increased from 62.3 ± 5.2% to 80.2 ± 3.3% (P < 0.05) of control. Vabdominal increased at a rate of 1.8 ± 0.9 ml·kg(-1)·min(-1) (P < 0.01), reversing the ANG II effects. In conclusion, BAT increases arterial conductance, decreases PAo, and increases venous capacitance even in the presence of powerful vasoactive drugs. Increasing venous capacitance may be an important effect of BAT in hypertension.

Wave reflections in the pulmonary arteries analysed with the reservoir-wave model.

Conventional haemodynamic analysis of pressure and flow in the pulmonary circulation yields incident and reflected waves throughout the cardiac cycle, even during diastole. The reservoir-wave model provides an alternative haemodynamic analysis consistent with minimal wave activity during diastole. Pressure and flow in the main pulmonary artery were measured in anaesthetized dogs and the effects of hypoxia and nitric oxide, volume loading and positive end-expiratory pressure were observed. The reservoir-wave model was used to determine the reservoir contribution to pressure and flow and once subtracted, resulted in 'excess' quantities, which were treated as wave-related. Wave intensity analysis quantified the contributions of waves originating upstream (forward-going waves) and downstream (backward-going waves). In the pulmonary artery, negative reflections of incident waves created by the right ventricle were observed. Overall, the distance from the pulmonary artery valve to this reflection site was calculated to be 5.7 ± 0.2 cm. During 100% O2 ventilation, the strength of these reflections increased 10% with volume loading and decreased 4% with 10 cmH2O positive end-expiratory pressure. In the pulmonary arterial circulation, negative reflections arise from the junction of lobar arteries from the left and right pulmonary arteries. This mechanism serves to reduce peak systolic pressure, while increasing blood flow.

High-frequency oscillatory ventilation versus conventional ventilation: hemodynamic effects on lung and heart.

Abstract High-frequency oscillatory ventilation (HFOV) may improve gas exchange in patients who are inadequately ventilated by conventional mechanical ventilation (CV); however, the hemodynamic consequences of switching to HFOV remain unclear. We compared the effects of CV and HFOV on pulmonary vascular conductance and left ventricular (LV) preload and performance at different airway and filling pressures. In anesthetized dogs, we measured LV dimensions, aortic and pulmonary artery (PA) flow, and mean airway ( AW) and pericardial pressures. Catheter-tip pressure manometers measured aortic, LV, left atrial, and PA pressures. The pericardium and chest were closed. At LV end-diastolic pressure (PLVED) = 5 mmHg and 12 mmHg, PEEP was varied (6 cm H2O, 12 cm H2O, and 18 cm H2O) during CV. Then, at airway pressures equal to those during CV, HFOV was applied at 4 Hz, 10 Hz, and 15 Hz. Increased AW decreased pulmonary vascular conductance. As cardiac output increased, conductance increased. At PLVED = 12 mmHg, conductance was greatest during HFOV at 4 Hz. LV preload (i.e., ALV, our index of end-diastolic volume) was similar during HFOV and CV for all conditions. At PLVED = 12 mmHg, SWLV was similar during CV and HFOV, but, at PLVED = 5 mmHg and AW 10 cm H2O, SWLV was lower during HFOV than CV. Compared to pulmonary vascular conductance at higher frequencies, at PLVED = 12 mmHg, conductance was greater at HFOV of 4 Hz. Effects of CV and HFOV on LV preload and performance were similar except for decreased SWLV at PLVED = 5 mmHg. These observations suggest the need for further studies to assess their potential clinical relevance.

Toward zero: deep sternal wound infection after 1001 consecutive coronary artery bypass procedures using arterial grafts: implications for diabetic patients.

OBJECTIVE: Coronary artery bypass graft (CABG) surgery with arterial conduits is considered optimal. A deterrent to bilateral internal thoracic artery (BITA) grafting is the risk of deep sternal wound infection (DSWI). We introduced infection prevention measures sequentially, attempting to reduce DSWIs. The aim was to determine (1) if the absence of DSWIs in the last 469 of 1001 consecutive operations was significant; (2) which measures explained the change; and (3) the impact of diabetes. METHODS: The measures included internal thoracic artery (ITA) skeletonization, no bone wax, wound irrigation, 1 observer per case, harmonic scalpel harvest of ITAs, vancomycin paste on sternal marrow, iodine-impregnated skin drapes, chlorhexidine-alcohol skin preparation, no BITA grafts in obese, diabetic women, more off-pump procedures, aseptic wound care, and marrow irrigation before sternal approximation. RESULTS: Mean age was 65±10.4 years, 78% were male, 34% had diabetes, and 34% were obese. The first 532 patients had 16 DSWIs (3%) and the subsequent 469 had none (P<.001). Analysis of the data suggested that the first 11 measures likely contributed to the absence of DSWI and less likely, the twelfth. Key measures were likely chlorhexidine-alcohol use and avoidance of BITAs in obese diabetic women who had a 10-fold higher DSWI rate than the other patients (21.4% vs 2.0%). Other diabetics, including obese men, had no increased risk of DSWI. CONCLUSIONS: The measures applied caused a substantial reduction in DSWIs. Key measures included the use of chlorhexidine-alcohol and avoidance of BITA grafting in obese diabetic females. These measures reduced DSWIs after BITA grafting in most diabetics.

Partitioning pulmonary vascular resistance using the reservoir-wave model.

The conventional determination of pulmonary vascular resistance does not indicate which vascular segments contribute to the total resistance of the pulmonary circulation. Using measurements of pressure and flow, the reservoir-wave model can be used to partition total pulmonary vascular resistance into arterial, microcirculation, and venous components. Changes to these resistance components are investigated during hypoxia and inhaled nitric oxide, volume loading, and positive end-expiratory pressure. The reservoir-wave model defines the pressure of a volume-related reservoir and the asymptotic pressure. The mean values of arterial and venous reservoir pressures and arterial and venous asymptotic pressures define a series of resistances between the main pulmonary artery and the pulmonary veins: the resistance of large and small arteries, the microcirculation, and veins. In 11 anaesthetized, open-chest dogs, pressure and flow were measured in the main pulmonary artery and a single pulmonary vein. Volume loading reduced each vascular resistance component, whereas positive end-expiratory pressure only increased microcirculation resistance. Hypoxia increased the resistance of small arteries and veins, whereas nitric oxide only decreased small-artery resistance significantly. The reservoir-wave model provides a novel method to deconstruct total pulmonary vascular resistance. The results are consistent with the expected physiological responses of the pulmonary circulation and provide additional information regarding which segments of the pulmonary circulation react to hypoxia and nitric oxide.

Alterations in aortic wave reflection with vasodilation and vasoconstriction in anaesthetized dogs.

BACKGROUND: Using the reservoir-wave approach, we studied wave propagation, reflection, and re-reflection in the canine aorta with administrations of sodium nitroprusside (NP) and methoxamine (Mtx). METHODS: In 8 anaesthetized dogs, excess pressures were calculated from pressure and flow measurements at 4 locations along the aorta; wave intensity analysis was employed to identify wavefronts and the type of waves. RESULTS: NP (intravenous; 14 µg/min) decreased mean aortic pressure from 80 ± 3 mm Hg to 48 ± 1 mm Hg; Mtx (intravenous; 10 µg/min) increased mean pressure from 80 ± 3 mm Hg to 104 ± 4 mm Hg. NP increased negative reflection near the kidneys (reflection coefficient: -0.33 vs -0.18; P < 0.01) and produced new negatively reflecting sites just beyond the arch and in the proximal femoral arteries, consistent with a vasodilating effects of nitrates on conducting arteries. Mtx negated negative reflection from near the kidneys (-0.02 vs -0.17; P < 0.01) and increased positive femoral reflection (0.38 vs 0.26; P < 0.01). The large reflected compression wave was re-reflected from the closed aortic valve to produce a prominent increase in middiastolic pressure in the distal aorta. CONCLUSIONS: The reservoir-wave approach explains decreasing diastolic pressure without positing waves that travel at near-infinite velocities and reveals the pressure changes that are uniquely due to wave motion.

Mechanism of loss of consciousness during vascular neck restraint.

Vascular neck restraint (VNR) is a technique that police officers may employ to control combative individuals. As the mechanism of unconsciousness is not completely understood, we tested the hypothesis that VNR simply compresses the carotid arteries, thereby decreasing middle cerebral artery blood flow. Twenty-four healthy police officers (age 35 ± 4 yr) were studied. Heart rate (HR), arterial pressure, rate of change of pressure (dP/dt), and stroke volume (SV) were measured using infrared finger photoplethysmography. Bilateral mean middle cerebral artery flow velocity (MCAVmean) was measured by using transcranial Doppler ultrasound. Neck pressure was measured using flat, fluid-filled balloon transducers positioned over both carotid bifurcations. To detect ocular fixation, subjects were asked to focus on a pen that was moved from side to side. VNR was released 1-2 s after ocular fixation. Ocular fixation occurred in 16 subjects [time 9.5 ± 0.4 (SE) s]. Pressures over the right (R) and left (L) carotid arteries were 257 ± 22 and 146 ± 18 mmHg, respectively. VNR decreased MCAVmean (R 45 ± 3 to 8 ± 4 cm/s; L 53 ± 2 to 10 ± 3 cm/s) and SV (92 ± 4 to 75 ± 4 ml; P < 0.001). Mean arterial pressure (MAP), dP/dt, and HR did not change significantly. We conclude that the most important mechanism in loss of consciousness was decreased cerebral blood flow caused by carotid artery compression. The small decrease in CO (9.6 to 7.5 l/min) observed would not seem to be important as there was no change in MAP. In addition, with no significant change in HR, ventricular contractility, or MAP, the carotid sinus baroreceptor reflex appears to contribute little to the response to VNR.

Volume loading reduces pulmonary vascular resistance in ventilated animals with acute lung injury: evaluation of RV afterload.

During mechanical ventilation, increased pulmonary vascular resistance (PVR) may decrease right ventricular (RV) performance. We hypothesized that volume loading, by reducing PVR, and, therefore, RV afterload, can limit this effect. Deep anesthesia was induced in 16 mongrel dogs (8 oleic acid-induced acute lung injury and 8 controls). We measured ventricular pressures, dimensions, and stroke volumes during positive end-expiratory pressures of 0, 6, 12, and 18 cmH(2)O at three left ventricular (LV) end-diastolic pressures (5, 12, and 18 mmHg). Oleic acid infusion (0.07 ml/kg) increased PVR and reduced respiratory system compliance (P < 0.05). With positive end-expiratory pressure, PVR was greater at a lower LV end-diastolic pressure. Increased PVR was associated with a decreased transseptal pressure gradient, suggesting that leftward septal shift contributed to decreased LV preload, in addition to that caused by external constraint. Volume loading reduced PVR; this was associated with improved RV output and an increased transseptal pressure gradient, which suggests that rightward septal shift contributed to the increased LV preload. If PVR is used to reflect RV afterload, volume loading appeared to reduce PVR, thereby improving RV and LV performance. The improvement in cardiac output was also associated with reduced external constraint to LV filling; since calculated PVR is inversely related to cardiac output, increased LV output would reduce PVR. In conclusion, our results, which suggest that PVR is an independent determinant of cardiac performance, but is also dependent on cardiac output, improve our understanding of the hemodynamic effects of volume loading in acute lung injury.

Transit-time flow predicts outcomes in coronary artery bypass graft patients: a series of 1000 consecutive arterial grafts.

OBJECTIVE: This study was undertaken to evaluate transit-time flow (TTF) as a tool to detect technical errors in arterial bypass grafts intra-operatively and predict outcomes. METHODS: TTF's three parameters, pulsatility index (PI, index of resistance), flow (cc min(-1)) and diastolic filling (DF, proportion of diastole with coronary flow), were measured in 990/1000 (99%) of arterial grafts in 336 consecutive patients, prospectively enrolled in a database. Grafts were revised when TTF findings supported the otherwise suspected graft malfunction. If no other signs/suspicion of graft malfunction existed (normal electrocardiogram (EKG), stable haemodynamics and unchanged ventricular function on trans-oesophageal echocardiography (TEE)), and the PI was >5, grafts were not revised. Major adverse cardiac events (MACEs: recurrent angina, perioperative myocardial infarction, postoperative angioplasty, re-operation and/or perioperative death) were related to TTF measurements. RESULTS: The average number of grafts per patient was 3.02, of which 99% were arterial. Satisfactory grafts were achieved in 916/990 (93%) of the grafts, with flows from 34 to 61 cc min(-1), PI < or =5 and DF of 62-85%. Fourteen conduits, 20 grafts (2%) suspected to be problematic, were revised. Patients were divided into two groups: 277 (82%) with at least one graft with PI < or =5 and 59 (18%) with a PI >5. MACE occurred in 25 (7.4%) patients--15/277 patients with a PI < or =5 (5.4%) and 10/59 with a PI >5 (17%, p=0.005). Mortality following non-emergent surgery was significantly higher in patients with a PI >5 (5/54, 9%) than in patients with a PI < or =5 (5/250, 2%, p=0.02). Flow and DF were not predictive of outcomes. CONCLUSION: A high PI predicts technically inadequate arterial grafts during surgery--even if all other intra-operative assessments indicate good grafts; it also predicts outcomes, particularly mortality.

Transmural temporospatial left ventricular activation during pacing from different sites: potential implications for optimal pacing.

AIMS: Previous studies showed that right ventricular (RV) endocardial pacing can be deleterious even in individuals with initially normal left ventricular (LV) function. The mechanism(s) by which RV endocardial pacing may cause LV dysfunction is unknown. This study compares the temporospatial LV transmyocardial activation profiles during sinus rhythm with normal His/Purkinje conduction vs. currently utilized and proposed cardiac pacing sites. METHODS AND RESULTS: Mongrel dogs were instrumented with transmural electrodes that tracked transmyocardial activation sequences at five sites in the LV. Pacing/recording catheters were positioned in the RV apex and on the RV and LV sides of the ventricular septum. An epicardial pacing electrode was also sewn to the mid-lateral LV epicardium. Electrograms were recorded during sinus rhythm and pacing from the RV endocardium, LV septum, LV epicardium and during biventricular pacing. Compared to normal sinus/His/Purkinje rhythm (NSR), RV endocardial pacing significantly (P < 0.05) prolonged transmural activation (NSR endocardium 6.1 +/- 1 ms vs. RV endocardium 23.0 +/- 2.6 ms). The highly ordered temporospatial pattern of transmural activation during sinus rhythm was replaced with dispersion and intermingling of endo-, mid-, and epicardial activation. LV epicardial and biventricular pacing did not correct these abnormalities. Only LV septal pacing achieved the transmural and transseptal activation sequences similar to sinus rhythm. CONCLUSION: Clinically utilized pacing modalities, including biventricular pacing, cause abnormal transmyocardial activation. LV septal pacing results in transmyocardial activation patterns that closely resemble those seen in sinus rhythm.

Contrast echocardiography accurately predicts myocardial perfusion before angiography during acute myocardial infarction.

OBJECTIVES: To determine whether myocardial contrast echocardiography (MCE) can quickly and accurately assess myocardial perfusion and infarct-related artery (IRA) patency before emergency angiography during acute myocardial infarction (AMI). BACKGROUND: Despite encouraging experimental and clinical studies, the reliability and practicality of MCE in predicting IRA patency during AMI before angiography has not been proven. METHODS: Two-dimensional echocardiography and MCE were performed in 51 patients with AMI just before emergency angiography. With knowledge of the electrocardiogram findings and regional wall motion, myocardial perfusion was assessed to predict IRA patency. RESULTS: Myocardial perfusion studies were adequate for interpretation in 40 patients. An occluded IRA was predicted in 28 patients; the artery was occluded in 22 patients, and six patients had Thrombolysis In Myocardial Infarction (TIMI) grade 2 flow or less. A patent IRA was predicted in 12 patients; eight patients had TIMI grade 3 flow, one patient had TIMI grade 2 flow and the IRA was occluded in three patients. In one of the three patients, the appropriate view was not obtained. In another patient, collateral flow was adequate for near-normal regional wall motion, and in the last, the findings suggested reperfusion of the proximal artery with distal embolic occlusion. Taken together, MCE accurately predicted either TIMI grade 2 flow or less, or TIMI grade 3 flow in 36 of 40 patients. Sensitivity was 87.5%, specificity and positive predictive value were 100% and negative predictive power was 66.7% (P<0.001). CONCLUSIONS: MCE, together with the electrocardiogram and regional wall motion, can be used to quickly and reliably predict IRA patency early during AMI and may be useful to facilitate a management strategy.

Effects of an enhanced secondary prevention program for patients with heart disease: a prospective randomized trial.

BACKGROUND: Secondary prevention medications in cardiac patients improve outcomes. However, prescription rates for these drugs and long-term adherence are suboptimal. OBJECTIVE: To determine whether an enhanced secondary prevention program improves outcomes. METHODS: Hospitalized patients with indications for secondary prevention medications were randomly assigned to either usual care or an intervention arm, in which an intensive program was used to optimize prescription rates and long-term adherence. Follow-up was 19 months. RESULTS: A total of 2643 patients were randomly assigned in the study; 1342 patients were assigned to usual care and 1301 patients were assigned to the intervention arm. Prescription rates were near optimal except for lipid-lowering medications. Rehospitalization rates per 100 patients were 136.2 and 132.6 over 19 months in the usual care and intervention groups, respectively (P=0.59). Total days in hospital per patient were similar (10.9 days in the usual care group versus 10.2 days in the intervention group; P not significant). Crude mortality was 6.2% and 5.5% in the usual care and intervention groups, respectively, with no significant difference (P=0.15) in overall survival. Post hoc analysis suggested that after the study team became experienced, days in hospital per patient were reduced by the program (11.1+/-0.91 and 8.9+/-0.61 in the usual care and intervention groups, respectively; P<0.05). CONCLUSIONS: The intervention program failed to improve outcomes in the present study. One explanation for these results is the near optimal physician compliance with guidelines in both groups. It is also possible that a substantial learning curve for the staff was involved, as suggested by the reduction in total days in hospital in the intervention patients during the second part of the study.