Doppler cardiac output and left ventricular performance after cardiac surgery. Pulsed Doppler ascending aorta and pulmonary blood flows and left ventricular function using implanted microprobes.

We have developed novel implantable Doppler microprobes to monitor beat-by-beat stroke volume and cardiac output (CO) after cardiac surgery. In 11 adults undergoing either coronary artery bypass grafting (n = 6) or valve replacement (n = 5), Doppler microprobes were implanted on the ascending aorta or the main pulmonary artery to measure aortic blood flow (ABF) or pulmonary artery blood flow (PBF). The diameters of both vessels were determined before surgery using two-dimensional echocardiography. Stroke volume was obtained from velocity tracings measured by a 4-MHz zero-crossing pulsed Doppler flowmeter. Simultaneous measurements of Doppler and thermodilution CO (TDCO) were compared. We found the following: ABF = 1.03 TDCO - 0.22 L/min (r = 0.89); while PBF = 0.69 TDCO - 1.24 L/min (r = 0.75). Furthermore, peak flow velocity and maximum acceleration of blood in the ascending aorta were measured after inotropic stimulation with dobutamine; both values increased significantly from control values (25.2 +/- 6.1 percent and 44.6 +/- 8.6 percent, respectively, at 7.5 micrograms/kg/min). We conclude that implanted aortic Doppler microprobes provide a sensitive and reliable method to measure aortic blood flow velocity after surgery and then allow monitoring of stroke volume and CO and analysis of left ventricular function after cardiac surgery.

Interactions between hemodynamic and hormonal modifications during PEEP-induced antidiuresis and antinatriuresis.

The interactions between hemodynamic and hormonal modifications during antidiuresis and antinatriuresis induced by positive end-expiratory pressure (PEEP) were studied in six patients under 15 cm H2O PEEP before PEEP and after the addition of lower body positive pressure (LBPP) to PEEP (PEEP+LBPP). We measured or calculated the following: cardiac index, systemic arterial, right atrial, pulmonary arterial, and pulmonary artery occlusive pressures; indexed renal blood flow (iodohippurate 131 sodium clearance); total blood volume (chromium 51 radiolabeled RBCs); glomerular filtration rate; urinary output; fractional excretion of sodium (FE Na+); plasma concentrations of antidiuretic hormone (ADH), plasma renin activity (PRA), norepinephrine and epinephrine; urinary concentration of PGE2 (PGE2u). Although LBPP application corrected PEEP deleterious effects on systemic and renal hemodynamics, sustained fall in Vu and in FE Na+ were observed. Antidiuresis was not due to ADH release. Sympathetic activation and high PRA appeared the main determinants of renal function alterations in PEEP ventilation.

Angiotensin-converting enzyme inhibitor therapy improves respiratory muscle strength in patients with heart failure.

STUDY OBJECTIVES: Respiratory muscle strength has been shown to be reduced in patients with chronic heart failure. The purpose of this prospective study was to determine whether long-term therapy with the angiotensin-converting enzyme (ACE) inhibitor perindopril improves respiratory muscle strength in patients with chronic heart failure. PATIENTS AND METHODS: Eighteen patients with stable chronic heart failure were administered perindopril, 4 mg/d, in addition to their standard therapy for a period of 6 months. Fourteen patients completed the study. Maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax) expressed in percentage of predicted values, left ventricular ejection fraction (LVEF) determined by means of two-dimensional echocardiography, and pulmonary volumes were obtained before and after therapy. MEASUREMENTS AND RESULTS: As compared to baseline, there was a significant increase in both PImax and PEmax after therapy (57 +/- 27% predicted vs 78 +/- 36% predicted and 62 +/- 20% predicted vs 73 +/- 15% predicted, respectively; each p < 0.05). LVEF increased (34 +/- 5% vs 41 +/- 10%; p < 0.05); functional class improved by > or = 1 New York Heart Association (NYHA) class in five patients. There were no changes in pulmonary volumes. No correlation was found between changes in PImax and PEmax and changes in either LVEF or NYHA functional class. CONCLUSIONS: In patients with chronic heart failure, long-term therapy with the ACE inhibitor perindopril improved respiratory muscle strength, as indicated by significant increases in PImax and PEmax.

Portal and hepatic arterial blood flow measurements of human transplanted liver by implanted Doppler probes: interest for early complications and nutrition.

Hepatic artery thrombosis and early acute rejection are severe complications of orthotopic liver transplantation (OLT). Their rapid detection is most desirable. The purpose of this study was to assess the usefulness of monitoring hepatic artery (HABF) and portal vein (PVBF) blood flows during the first week after OLT. At the end of operation, microprobes were sutured to the vessels, and their connecting tubes were externalized and connected to a pulsed Doppler flowmeter operating at 8 MHz. In 10 patients (ages ranged from 2 to 54 years) of 106, measurements of HABF and PVBF were done during alternative clamping of both vessels and before and after abdominal closure, every 12 hours during 7 days, and at day 7, before and after a 150 gm carbohydrate meal. At day 7 the probes were pulled out by gentle traction without complication, and all patients were allowed to go home. Reciprocal increase of flow during selective clamping was only observed for HABF (+45.8% +/- 47.6%; p less than 0.01). Abdominal closure decreased both HABF and PVBF by 13.8%, p less than 0.01, and 26%, p less than 0.05, respectively. In seven cases no significant variation of HABF and PVBF was observed during 7 days. In two patients with histologically confirmed early acute rejection, a marked decrease of diastolic HABF, without modification in PVBF, was the first manifestation and was rapidly corrected by boluses of steroids. In one patient disappearance of systolic and diastolic HABF led us to diagnose an arterial obliteration caused by a plicature, which was successfully surgically treated in the emergency department. In all patients, after oral ingestion of the carbohydrate meal, and only after this type of diet, a significant and deep decrease (-87%, p less than 0.001) of HABF was observed between 7 and 120 minutes without any change in PVBF. Such an effect was not observed in control patients. We conclude that this Doppler flowmetric technique with implantable microprobes is useful for rapid diagnosis of and strategy in treating early complications and is a new tool for pathophysiologic study of OLT consequences.

Rat diaphragm during postnatal development. I. Changes in distribution of muscle fibre type and in oxidative potential.

The changes occurring in the histochemical characteristics of the rat diaphragm during the postnatal period were examined. Fibre-type distribution, fibre oxidative capacity, i.e. succinate-dehydrogenase (SDH) activity, and cross-sectional area were compared in the costal (COS) and crural (CRU) regions, and across their abdominal and thoracic surfaces. The proportions of type I and IIb fibres in both COS and CRU increased with age, while the proportion of type IIa fibres progressively decreased. For COS, fibre distribution was homogeneous over the entire muscle and did not change after 4 weeks. For CRU, it was heterogeneous with a higher proportion of type I fibres on the thoracic surface as from the first week. All fibre types significantly increased in cross-sectional area between 1 and 8 weeks, with no significant differences in COS and CRU. Mean SDH activity did not differ between COS and CRU or across the muscles. Mean SDH activities-were low and identical in all fibre types at birth, and then increased, peaking at the 6th week in type I and IIa fibres. When total muscle fibre oxidative capacity was calculated from an index including fibre-type proportion, cross-sectional area and mean SDH activity, it was significantly higher at 1 than at 8 weeks after birth; this might have functional implications for the newborn.

Rat diaphragm during postnatal development. II. Resistance to low- and high-frequency fatigue.

The effects on the rat diaphragm of fatigue induced by low- and high-frequency stimulation (at 5 Hz for 1.5 min and 75 Hz for 1 min) were examined during postnatal development. Experiments were performed on isolated costal diaphragm strips. Before stimulation, twitch contraction time and half relaxation time were longest in the neonate and decreased significantly between weeks 1 and 6. Correspondingly, the specific twitch tension (corrected for cross-sectional area) increased progressively with age. After either low- or high-frequency fatigue, the force recovery was complete in 1- and 2-week-old rats, whereas the force production progressively decreased in older rats. In addition, the neonate diaphragm further enhanced its force selectively after high-frequency fatigue. It is concluded that the rat diaphragm is comparably resistant to fatigue during the early postnatal period, whether fatigue is induced by low- or by high-frequency stimulation. This suggests that postnatal changes in diaphragm contractile and fatigue properties may be related to changes in the process of force production. The possibility is discussed that a higher total muscle oxidative potential and the mechanisms leading to force potentiation in the neonate might explain the fatigue resistance.

cAMP-dependent modulation of L-type calcium currents in mouse diaphragmatic cells.

The regulation of calcium channels by cAMP-dependent phosphorylation was investigated in the diaphragm muscle. Experiments were performed on dissociated costal diaphragmatic cells from 16- to 17-day-old fetal mice. The ionic current through calcium channels was measured using the whole cell clamp technique with barium as the charge carrier. A depolarizing pulse delivered from a holding potential of -80 mV elicited a low-threshold dihydropyridine (DHP)-insensitive T-type current and a high-threshold DHP-sensitive L-type current. Agents that either increase intracellular cAMP levels (forskolin, 10(-4) M, and dibutyryladenosine 3'-5' cyclic monophosphate, 10(-4) M) or inhibit cAMP degradation (theophylline, 10(-4) M) produced relative increases in L-type current amplitude of 24.4 +/- 13.8%, 13.4 +/- 4.6%, and 15.9 +/- 2.8% (p < 0.05), respectively. Current intensity increased after application of the beta-adrenergic agonist isoproterenol (10(-5) M, 16.5 +/- 3.6%, P < 0.005). None of these agents affected the T-type current. These results suggest that L-type calcium channel activities of the diaphragm muscle are regulated by cAMP-dependent phosphorylation.

Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction.

Background. The gas nitric oxide (NO) is an important endothelium-derived relaxing factor, inactivated by rapid combination with heme in hemoglobin. Methods and Results. Awake spontaneously breathing lambs inhaled 5-80 ppm NO with an acutely constricted pulmonary circulation due to either infusion of the stable thromboxane endoperoxide analogue U46619 or breathing a hypoxic gas mixture. Within 3 minutes after adding 40 ppm NO or more to inspired gas, pulmonary hypertension was reversed. Systemic vasodilation did not occur. Pulmonary hypertension resumed within 3-6 minutes of ceasing NO inhalation. During U46619 infusion pulmonary vasodilation was maintained up to 1 hour without tolerance. In the normal lamb, NO inhalation produced no hemodynamic changes. Breathing 80 ppm NO for 3 hours did not increase either methemoglobin or extravascular lung water levels nor modify lung histology compared with control lambs. Conclusions. Low dose inhaled NO (5-80 ppm) is a selective pulmonary vasodilator reversing both hypoxia- and thromboxane-induced pulmonary hypertension in the awake lamb [corrected].

Thoracic epidural anesthesia increases diaphragmatic shortening after thoracotomy in the awake lamb.

BACKGROUND: Prolonged inhibition of diaphragmatic function occurs after thoracic and upper abdominal surgery. It was hypothesized that thoracic epidural anesthesia on the day after a thoracotomy could block inhibitory neural pathways and increase the shortening of costal and crural diaphragmatic segments. METHODS: Pairs of sonomicrometer crystals were implanted into the costal and crural regions of the diaphragm through a right lateral thoracotomy in 14 30-kg, 4-5-month-old lambs. One day after surgery, a thoracic epidural catheter was placed at the T8-T9 level. Regional diaphragmatic shortening normalized to end-expiratory length (%LFRC), was measured by sonomicrometry in these awake lambs. Changes in gastric (delta Pgas), esophageal (delta Pes), and transdiaphragmatic (delta Pdi) pressures were measured with transnasal balloon catheters. End-tidal carbon dioxide (FETCO2), costal and crural electromyogram (Edi), and tidal volume (VT) were measured. Inductance plethysmography was used in four lambs to assess relative contributions of the rib cage and abdomen to VT. Control values were obtained during quiet breathing and while rebreathing at up to 10% FETCO2. To block thoracic dermatomes, 1% or 2% lidocaine was injected through the epidural catheter. Measurements were repeated after each lidocaine injection. RESULTS: There was no change of resting length with 1% lidocaine; costal resting length increased by 22% with 2% lidocaine. After 2% lidocaine, costal %LFRC increased from control both during quiet breathing (8.7 +/- 0.7 to 18.1 +/- 1, mean +/- SEM%) and at FETCO2 10% (22.1 +/- 2 to 33.7 +/- 3%). VT during quiet breathing was unchanged after 1% lidocaine but increased from 235 +/- 16 to 283 +/- 28 ml after 2% lidocaine. At 10% FETCO2, delta Pdi was unchanged after 1% lidocaine and decreased from 36.5 +/- 4.3 to 26.3 +/- 4.9 cmH2O after 2% lidocaine. Regional delta Edi was unchanged with both 1% and 2% lidocaine at rest and during carbon dioxide rebreathing. Plethysmography in three lambs showed a reduction in rib cage contribution to tidal volume with 2% lidocaine during quiet breathing. CONCLUSIONS: Improved postoperative tidal volume and diaphragmatic shortening after thoracic epidural blockade may be due to changes of chest wall conformation and resting length and a shift of the workload of breathing from the rib cage to the diaphragm caused by intercostal muscle paralysis.

Effects of digoxin on regional diaphragm function after thoracotomy in awake sheep.

The effects of digoxin on diaphragmatic contraction were studied in 12 sheep, within 6 days after a right thoracotomy, during the period of intense diaphragmatic inhibition. Diaphragmatic function was assessed by implanting sonomicrometry crystals and electromyographic (EMG) electrodes in both the costal and crural diaphragmatic regions. Awake sheep were studied before and after intravenous digoxin (0.04 mg/kg) during both quiet breathing (QB) and during CO2 rebreathing, until the fractional concentration of expired CO2 (FETCO2) reached 0.10. After digoxin infusion, during both QB and at FETCO2 of 0.10, esophageal and transdiaphragmatic pressures increased (P < 0.05). After digoxin infusion no changes were measured for end-expiratory resting length, shortening fraction, shortening velocity or EMG activity of either diaphragmatic segment or for respiratory frequency, ventilation, tidal volume and FETCO2. We conclude that intravenous digoxin given to awake sheep after a thoracotomy increases Pdi, but does not alter diaphragmatic shortening nor alter the level of diaphragmatic activation either during QB or at FETCO2 of 0.10.

Hemodynamic and gas exchange responses to infusion of acetylcholine and inhalation of nitric oxide in patients with chronic obstructive lung disease and pulmonary hypertension.

To investigate endothelium-dependent and endothelium-independent nitric oxide (NO) mediated pulmonary vasodilation in patients with chronic obstructive lung disease (COLD), we examined the responses to incremental infusion rates of acetylcholine (ACh) or inhaled NO on hemodynamic and gas exchange. In 13 patients, ACh (15 mg/min) decreased pulmonary artery pressure (Ppa) from 31 +/- 1 to 28 +/- 1 mm Hg (p < 0.01) and systemic arterial pressure while increasing cardiac index from 3.7 +/- 0.4 to 4.7 +/- 0.4 L/min/m2 (p < 0.01). Inhaling 40 parts per million (ppm) NO decreased Ppa from 32 +/- 1 to 26 +/- 1 mm Hg (p < 0.001) with no associated hemodynamic change. ACh reduced PaO2 from 57 +/- 3 to 48 +/- 2 mm Hg (p < 0.01) and increased venous admixture (QVA/QT) from 35 +/- 3 to 45 +/- 3% (p < 0.01). Inhaling 40 ppm NO increased PaO2 from 57 +/- 3 to 60 +/- 3 mm Hg (p < 0.01) and decreased QVA/QT from 36 +/- 3 to 32 +/- 3% (p < 0.01). Pulmonary vascular resistance changes were similar in response to 40 ppm NO or 15 mg/min ACh. In COLD patients, ACh produces both pulmonary and systemic vasodilation but impairs arterial oxygenation whereas inhaled NO induces selective pulmonary vasodilation while improving gas exchange. The resistance to ACh in some patients could be related to pulmonary endothelial dysfunction.

Diaphragmatic shortening after thoracic surgery in humans. Effects of mechanical ventilation and thoracic epidural anesthesia.

BACKGROUND: Diaphragmatic function is believed to be inhibited after thoracic surgery and may be improved by thoracic epidural anesthesia. METHODS: Diaphragmatic function after a thoracotomy was monitored by implanting one pair of sonomicrometry crystals and two electromyogram (EMG) electrodes on the costal diaphragm of six patients undergoing an elective pulmonary resection. Crystals and EMG electrodes remained in place for 12-24 h. RESULTS: During mechanical ventilation, costal diaphragmatic length (as a percent of rest length; %LFRC) decreased passively as tidal volume (VT) increased (%LFRC = 2.81 + 1.12 x 10(-2) VT (ml), r = 0.99). During spontaneous ventilation, the costal shortening (2.1 +/- 2.3 %LFRC) was less than during mechanical ventilation (7.9 +/- 3.0 %LFRC, P < 0.05) at the same VT. Comparing spontaneous ventilation before and 30 min after thoracic epidural anesthesia, there were increases of VT (390 +/- 78 to 555 +/- 75 ml), vital capacity (1.37 +/- 0.16 to 1.68 +/- 0.21 l), and esophageal (-8.5 +/- 1.5 to -10.6 +/- 1.7 cmH2O), gastric (-0.7 +/- 0.8 to +0.8 +/- 0.8 cmH2O), and transdiaphragmatic (7.7 +/- 1.5 to 11.5 +/- 1.9 cmH2O) pressures, but diaphragmatic EMG and shortening fraction remained constant. In three of six patients, epidural anesthesia produced paradoxical segment lengthening upon inspiration. CONCLUSIONS: Thoracotomy and pulmonary resection produce a marked reduction of active diaphragmatic shortening, which is not reversed by thoracic epidural anesthesia despite improvement of other indices of respiratory function.

Inhaled nitric oxide. A selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep.

Nitric oxide (NO) has recently been discovered to be an important endothelium-derived relaxing factor and produces profound relaxation of vascular smooth muscle. To learn if NO could be a potent and selective pulmonary vasodilator, NO was inhaled by 16 awake lambs in an attempt to reduce the increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) induced by either the infusion of an exogenous pulmonary vasoconstrictor (the thromboxane analog U46619) or the endogenous release of thromboxane that occurs during the neutralization of heparin anticoagulation by protamine sulfate. Inhaling greater than or equal to 40 ppm of NO during a continuous U46619 infusion returned the PAP to a normal value, without affecting systemic blood pressure or vascular resistance. Pretreatment with the cyclooxygenase inhibitor indomethacin before infusing U46619 did not reduce the pulmonary vasodilatory effect of inhaled NO, and we conclude that the dilatory effect of NO on the lung's circulation is independent of cyclooxygenase products such as prostacyclin. Continuously inhaling NO at 180 ppm did not significantly reduce the mean peak thromboxane B2 concentration at 1 min after protamine injection; however, the mean values of pulmonary hypertension and vasoconstriction at 1 min were markedly reduced below the levels in untreated heparin-protamine reactions. Breathing NO at lower concentrations (40-80 ppm) did not decrease the mean peak PAP and PVR at 1 min after protamine but decreased the PAP and PVR values at 2, 3, and 5 min below those of control heparin-protamine reactions. Intravenous infusion of nitroprusside completely prevented the transient increase of PAP and PVR during the heparin-protamine reaction; however, marked concomitant systemic vasodilation occurred. Inhaled NO is a selective pulmonary vasodilator that can prevent thromboxane-induced pulmonary hypertension during the heparin-protamine reaction in lambs and can do so without causing systemic vasodilation.