Mean Perfusion Pressure Research Articles

Femoral artery pressures are more reliable than radial artery pressures on initiation of cardiopulmonary bypass

Objective To compare radial and femoral artery perfusion pressure during initiation and various stages of cardiopulmonary bypass (CPB).Design Prospective study.Setting The cardiac center of a tertiary referral teaching institute.Participants Sixty consecutive patients of all ages undergoing a variety of cardiac operations.Interventions Radial and femoral arterial pressures were measured in all patients on the same transducer, from the beginning to end of CPB.Measurements and Main Results Mean perfusion pressures on CPB measured at the femoral artery at 1, 5, 10, and 15 minutes of CPB were 38.4 ± 3.6, 46.2 ± 3.1, 49.7 ± 3.9, and 52.8 ± 4.1 mmHg and were significantly greater than the corresponding radial artery pressures (29.9 ± 4.1, 35.3 ± 6.1, 40.9 ± 4.8, and 41.8 ± 5.3 mmHg) (p < 0.001). At 30 minutes and 60 minutes of CPB, femoral artery pressures are higher (60.3 ± 8.8 mmHg and 66.4 ± 8.2 mmHg) compared with radial artery pressures (54.7 ± 6.9 mmHg and 59.6 ± 6.1 mmHg), but the difference is less significant (p < 0.05). On conclusion of CPB, mean femoral artery pressures (70.9 ± 6.7 mmHg) are greater than mean radial artery pressures (67.6 ± 8.1 mmHg) (NS).Conclusions Although radial artery pressures are more commonly monitored during cardiac surgery, femoral artery perfusion pressures are more reliable during the initial part of CPB, and routine monitoring of femoral artery pressures may prevent vasoconstrictor use on initiation of CPB.

Tracheoesophageal fistula from an indwelling endotracheal tube balloon: a report of two cases and review

Tracheoesophageal fistula (TEF) is a rare but potentially life-threatening complication of prolonged endotracheal intubation. Fewer than a dozen cases of cuff-induced TEF have been reported since 1975. 1 Hilgenberg AD Grillo HC. Acquired nonmalignant tracheoesophageal fistula. J Thorac Cardiovasc Surg. 1983; 85: 492-498 PubMed Google Scholar , 2 Marzelle J Dartevelle P Khalife J Rojas-Miranda A Chapelier A Levasseur P. Surgical management of acquired post-intubation tracheo-oesophageal fistulas: 27 patients. Eur J Cardiothorac Surg. 1989; 3: 499-502 Crossref PubMed Scopus (46) Google Scholar , 3 Tan KK Lee JK Sarvesvaran R. Acquired tracheoesophageal fistula following tracheal intubation in a burned patient. Burns. 1993; 19: 360-361 Abstract Full Text PDF PubMed Scopus (8) Google Scholar , 4 Amodei C Pompili L Cianconi G Gaddi M Giuliani A Biddau A. Description of a case of tracheoesophageal fistula following endotracheal intubation. Minerva Anestesiol. 1987; 53: 651-653 PubMed Google Scholar , 5 Wimmer-Greinecker G Gross C Mair R Klima U Harringer W Brucke P. Coronary disease and tracheal stenosis with tracheo-oesophageal fistula: a combined surgical procedure. Cardiovasc Surg. 1998; 2: 226-228 Google Scholar , 6 Flege JB. Tracheoesophageal fistula caused by cuffed tracheostomy tube. Ann Surg. 1967; 166: 153-156 Crossref PubMed Scopus (39) Google Scholar Local tracheal mucosal irritation from the endotracheal tube balloon (ETB) occurs when balloon pressures exceed mean capillary perfusion pressure of 20 mm Hg. 7 Kamen JM Wilkinson CJ. A new low-pressure cuff for endotracheal tubes. Anesthesiology. 1971; 34: 482-485 Crossref PubMed Scopus (31) Google Scholar , 8 Thomas AN. The diagnosis and treatment of tracheoesophageal fistula caused by cuffed tracheal tubes. J Thorac Cardiovasc Surg. 1973; 65: 612-619 PubMed Google Scholar , 9 MacKenzie CF Klose S Browne DRG. A study of inflatable cuffs on endotracheal tubes. Br J Anaesth. 1976; 48: 105-109 Crossref PubMed Scopus (21) Google Scholar Indwelling rigid nasogastric tubes (NGT) have long been known to exacerbate esophageal mucosal degradation and necrosis with resultant fistula formation. 7 Kamen JM Wilkinson CJ. A new low-pressure cuff for endotracheal tubes. Anesthesiology. 1971; 34: 482-485 Crossref PubMed Scopus (31) Google Scholar , 8 Thomas AN. The diagnosis and treatment of tracheoesophageal fistula caused by cuffed tracheal tubes. J Thorac Cardiovasc Surg. 1973; 65: 612-619 PubMed Google Scholar , 9 MacKenzie CF Klose S Browne DRG. A study of inflatable cuffs on endotracheal tubes. Br J Anaesth. 1976; 48: 105-109 Crossref PubMed Scopus (21) Google Scholar , 10 Geha AS Seegers JV Kodner IJ Lefrak S. Tracheoesophageal fistula caused by cuffed tracheal tube: successful treatment by tracheal resection and primary repair with four-year follow-up. Arch Surg. 1978; 113: 338-340 Crossref PubMed Scopus (14) Google Scholar , 11 Lewis FR Schlobohm RM Thomas AN. Prevention of complications from prolonged tracheal intubation. Am J Surg. 1978; 135: 452-457 Abstract Full Text PDF PubMed Scopus (119) Google Scholar The contributing factor for ETB-induced TEF include over-inflation of the ETB 12 Magill IW. Endotracheal anesthesia. Proc Roy Soc Med Sect Anesth. 1928; 22: 83-88 Google Scholar , 13 Cooper JD Grillo HC. Evolution of tracheal injury due to ventilatory assistance through cuffed tubes; a pathologic study. Ann Surg. 1969; 169: 334-338 Crossref PubMed Scopus (208) Google Scholar , 14 Kastanos N Estopa Miro R Marin Perez A Xaubet Mir A Augusti-Vidal A. Laryngotracheal injury due to endotracheal intubation: incidence, evolution, and predisposing factors. A prospective long-term study. Crit Care Med. 1983; 11: 362-367 Crossref PubMed Scopus (200) Google Scholar , 15 Belson TP. Cuff induced tracheal injury in dogs following prolonged intubation. Laryngoscope. 1983; 93: 549-555 PubMed Google Scholar , 16 Lev A Barzilay E. Synchronized intermittent mandatory insufflation of the endotracheal tube cuff. Intensive Care Med. 1983; 9: 291-293 Crossref PubMed Scopus (3) Google Scholar , 17 Whited RE. A prospective study of laryngotracheal sequelae in long-term intubation. Laryngoscope. 1984; 94: 367-377 Crossref PubMed Scopus (318) Google Scholar and prolonged intubation. 8 Thomas AN. The diagnosis and treatment of tracheoesophageal fistula caused by cuffed tracheal tubes. J Thorac Cardiovasc Surg. 1973; 65: 612-619 PubMed Google Scholar , 9 MacKenzie CF Klose S Browne DRG. A study of inflatable cuffs on endotracheal tubes. Br J Anaesth. 1976; 48: 105-109 Crossref PubMed Scopus (21) Google Scholar , 10 Geha AS Seegers JV Kodner IJ Lefrak S. Tracheoesophageal fistula caused by cuffed tracheal tube: successful treatment by tracheal resection and primary repair with four-year follow-up. Arch Surg. 1978; 113: 338-340 Crossref PubMed Scopus (14) Google Scholar , 11 Lewis FR Schlobohm RM Thomas AN. Prevention of complications from prolonged tracheal intubation. Am J Surg. 1978; 135: 452-457 Abstract Full Text PDF PubMed Scopus (119) Google Scholar

Enhanced expression of inducible nitric oxide synthase without vasodilator effect in chronically infected lungs.

We hypothesized that abnormal ventilation-perfusion matching in chronically infected lungs was in part due to excess nitric oxide (NO) production after upregulation of inducible NO synthase (iNOS) expression. Rats were anesthetized and inoculated intratracheally with Pseudomonas aeruginosa incorporated into agar beads (chronically infected) or with sterile agar beads (placebo inoculated) and killed 10-15 days later. Immunohistochemistry demonstrated increased expression of iNOS and reduced expression of endothelial NOS (eNOS) in chronically infected compared with placebo-inoculated or noninoculated lungs. In isolated lungs from chronically infected rats, NOS inhibition with N(omega)-nitro-L-arginine methyl ester increased the mean perfusion pressure (14.4 +/- 2.7 mmHg) significantly more than in the placebo-inoculated (4.8 +/- 1.0 mmHg) or noninoculated (5.3 +/- 0.8 mmHg) lungs (P < 0.01). Although the chronically infected lungs were more sensitive to NOS inhibition, further evidence suggested that the increased iNOS expression was not associated with enhanced iNOS activity. Selective inhibitors of iNOS did not produce an increase in vascular resistance similar to that produced by nonselective inhibitors. Accumulation of nitrate/nitrite in the perfusate of isolated lungs was unchanged by chronic infection. Thus although iNOS expression was increased in chronic pulmonary infection, iNOS activity in the intact lung was not. Nonetheless, endogenous NO production was essential to maintain normal vascular resistance in these lungs.

Impairment of nitric oxide-mediated relaxations in anaesthetized autoperfused streptozotocin-induced diabetic rats.

This work was designed to determine in vivo the influence of the metabolic control of streptozotocin-induced diabetic rats, measured by the levels of haemoglobin glycosylation in blood (HbA1c), on developing vascular endothelial dysfunction. For this, the vasoactive responses to basal and stimulated endothelial nitric oxide (NO) were studied using the technique of the anaesthetized autoperfused rat, analyzing the responses to acetylcholine (ACh) and N(G)-nitro-L-arginine methyl ester (L-NAME) in non-diabetic and diabetic rats with different degrees of metabolic control (four groups with HbA1c levels of 5.5-7.4%, 7.5-9.4%, 9.5-12%, and >12%, respectively). When administered over a noradrenaline-induced vasopressor tone, ACh (0.25, 0.75, 2.5, 7.5 and 25 microg kg(-1)) induced dose-dependent vasodilatatory responses in all rat groups, reducing both mean arterial pressure and perfusion pressure of the left hindlimb. These responses were similar in non-diabetic and in diabetic rats with good metabolic control (HbA1c 5.5-7.4%), while diabetic rats with levels of HbA1c higher than 7.5% showed significantly lower vasodilatatory responses to ACh. In untreated diabetic rats, the relaxant responses evoked by the NO donor sodium nitroprusside were also impaired. On the other hand, increasing doses of L-NAME (0.1 to 10 mg kg(-1)) enhanced both mean arterial pressure and left hindlimb perfusion pressure in diabetic and non-diabetic rats. As with ACh, the responses to L-NAME were significantly reduced in diabetic rats with HbA1c levels higher than 7.5%. To determine the mechanism underlying the NO-mediated endothelial dysfunction, the responses to ACh in untreated diabetic rats (HbA1c >12%) were studied in the presence of the NO substrate L-arginine, in the presence of the oxygen-derived free radical scavenger superoxide dismutase (SOD), or in the presence of both compounds. Both L-arginine and SOD produced a partial improvement of the ACh-induced vasodilatatory responses, but the effects of these agents were not additive. In this group of animals, SOD also induced a partial recovery of the L-NAME-evoked vasoconstrictions. In non-diabetic and untreated diabetic rats, the plasma levels of NO derivatives and arginine were measured. No significant differences were obtained in the amount of nitrites plus nitrates, while plasma levels of arginine were markedly reduced in the untreated diabetic animals. The results indicate that the endothelial dysfunction associated to diabetes is closely related to the level of metabolic control of the disease. Therefore, it is possible to establish a threshold for developing endothelium impairment from percentages of HbA1c higher than 7.5%. As the responses to the NO synthase blocker L-NAME were analogously impaired, it is reasonable to suggest that diabetic endothelial dysfunction is related to the interference with mechanisms linked both to stimulated and basal production of NO. We suggest that this interference is partially due to a deficit in the substrate availability for NO and to an increased generation of superoxide anions.

Central nervous system effects of cardiopulmonary bypass

Background. The spectrum of approaches to the issue of brain injury in cardiac surgical practice ranges from refusal to acknowledge that the problem exists to an overemphasis on cerebral risks that can unduly frighten patients. An appropriate approach to therapeutic and preventive strategies requires a fitting sense of proportion and an understanding of the mechanisms of cerebral injury. Methods. This article reviews the incidence and severity of cerebral injury during cardiopulmonary bypass, the identification of high-risk patients, and the mechanisms of injury, including hypoperfusion, microemboli, and inflammatory response. It discusses the influences of alpha-stat and pH-stat strategies on cerebral blood flow during cardiopulmonary bypass; the use of retinal angiography to image the retinal circulation, thus providing a window on the cerebral microcirculation during bypass; magnetic resonance imaging evidence of an inflammatory response in the brain during bypass; and current efforts to gain better understanding of the molecular mechanisms involved in the inflammatory response. Results. The current incidence of stroke during cardiopulmonary bypass is somewhat lower than in the 1980s but still remains a significant problem. Levels of cognitive impairment also are unacceptably high. Recognized predictors enable us to identify patients at particularly high risk of stroke. Hypertensive patients are particularly susceptible to ischemic injury during bypass and should be perfused at mean perfusion pressures higher than those for normotensive patients. Under conditions of hypothermia, a pH-stat strategy causes loss of cerebral blood flow autoregulation, and the cerebral blood flow becomes pressure-passive. With both the pH-stat and alpha-stat strategies, cooling of the patient greatly increases the flow to metabolism ratio of the cerebral blood flow; however, this luxury perfusion brings to the brain not just an excess supply of oxygen but also an increased quantity of microemboli. Current investigative efforts are focused on the endothelial cell–leukocyte adhesion cascade, attempting to characterize β 2 and β 1 adhesion molecule expression in patients undergoing cardiac surgery. Hammersmith Hospital is about to complete a study of the effects of high-dose aprotinin on the inflammatory response pattern and on cerebral infarction. Conclusions. Further progress in the development of therapeutic and preventive strategies with respect to cerebral injury during cardiac bypass depends on an increase in the understanding of the mechanisms involved. Current strategies should include optimizing cerebral perfusion and minimizing macroembolic and microembolic damage. The possibility of modifying the systemic inflammatory response is the most interesting challenge of the next few years.

The relationship of vasogenic waves to ICP and cerebral perfusion pressure in head injured patients.

Slow vasogenic waves are characterised by sudden rises and falls in both the mean ICP and its cardiac pulsatile amplitude for periods of up to an hour. On reviewing the on-line computer records of a series of 200 consecutive head injured patients, some 650 waves with increases in mean ICP of at least 15 mm Hg were recognized. The mean ICP, pulsatile amplitude, perfusion pressure, arterial pressure and pulse rates which had been generated every minute were reviewed in each of a 100 randomly selected waves in the hopes of allocating them into defined groups according to precipitating factors. We had expected to find that the majority of waves were precipitated by a preceding fall in cerebral perfusion pressure as a result of a transient arterial hypotension. Only in 19 of the 100 waves did this sequence become apparent and in the remainder, no recognizable precipitating factors were found. In 21 of the records, there was a fall in ICP of at least 5 mm Hg before the onset of the pressure wave.

Cerebral blood flow velocity during induced ventricular fibrillation and ventricular tachycardia in humans

Mean cerebral blood flow velocity (CBFVMCA) and mean cerebral perfusion pressure (CPP) were investigated in five patients undergoing placement of an implantable cardioverter/defibrillator during 30 periods of induced pulseless ventricular tachycardia (VT) or induced ventricular fibrillation (VF) with a duration from 4 seconds to a maximum of 47 seconds. During VT (n=6) CBFVMCA decreased from 42 cm/sec (range: 32-60) to 20 cm/sec (range: 17-28) and during VF (n=24) it decreased from 44 cm/sec (range: 28-75) to 13 cm/sec (range: 10-15). CPP decreased from 66 mm Hg (range: 60-72) to 30 mm Hg (range: 27-38) during VT and from 63 mm Hg (range: 58-85) to 15 mm Hg (range: 8-25) during VF. Regardless of the type of underlying cardiac rhythm, transcranial Doppler ultrasonography revealed a constant forward blood flow in the middle cerebral artery during the early phase of induced VT or VF.

Reactivity of the isolated perfused rat tail vascular bed

Isolated segments of the perfused rat tail artery display a high basal tone when compared to other isolated arteries such as the mesenteric and are suitable for the assay of vasopressor agents. However, the perfusion of this artery in the entire tail has not yet been used for functional studies. The main purpose of the present study was to identify some aspects of the vascular reactivity of the rat tail vascular bed and validate this method to measure vascular reactivity. The tail severed from the body was perfused with Krebs solution containing different Ca2+ concentrations at different flow rates. Rats were anesthetized with sodium pentobarbital (65 mg/kg) and heparinized (500 U). The tail artery was dissected near the tail insertion, cannulated and perfused with Krebs solution plus 30 microM EDTA at 36 degrees C and 2.5 ml/min and the procedures were started after equilibration of the perfusion pressure. In the first group a dose-response curve to phenylephrine (PE) (0.5, 1, 2 and 5 micrograms, bolus injection) was obtained at different flow rates (1.5, 2.5 and 3.5 ml/min). The mean perfusion pressure increased with flow as well as PE vasopressor responses. In a second group the flow was changed (1.5, 2, 2.5, 3 and 3.5 ml/min) at different Ca2+ concentrations (0.62, 1.25, 2.5 and 3.75 mM) in the Krebs solution. Increasing Ca2+ concentrations did not alter the flow-pressure relationship. In the third group a similar protocol was performed but the rat tail vascular bed was perfused with Krebs solution containing PE (0.1 microgram/ml). There was an enhancement of the effect of PE with increasing external Ca2+ and flow. PE vasopressor responses increased after endothelial damage with air and CHAPS, suggesting an endothelial modulation of the tone of the rat tail vascular bed. These experiments validate the perfusion of the rat tail vascular bed as a method to investigate vascular reactivity.

Effect of the Duration of Room-Temperature Ischemia on Function of the Vascular Endothelium

The function of the vascular endothelium after storage at room temperature (24 degrees Celsius) for four, eight, and twenty-four hours was investigated with use of an ex vivo canine tibial perfusion model. Function was assessed in terms of changes in perfusion pressure and changes in the concentration of endothelin-1 in the venous effluent of the perfused tibiae. Endothelin-1 is a potent vasoconstrictor that is produced in low concentrations by normal endothelial cells and in increased concentrations by injured vascular endothelial cells. The mean perfusion pressures at flow rates of 1.0 and 1.5 milliliters per minute were significantly higher in the tibiae that had been stored for eight hours than in the tibiae that had been stored for four hours (p < 0.05), and they were significantly higher in the tibiae that had been stored for twenty-four hours than in the tibiae that had been stored for four or eight hours (p < 0.05). The increase in perfusion pressure with increasing duration of storage was associated with an increase in production of endothelin-1. The production of endothelin-1 in the tibiae that had been stored for eight hours (10.6 +/- 0.46 picograms per milliliter) was approximately ten times greater than that in the tibiae that had been stored for four hours (1.1 +/- 0.29 picograms per milliliter). The tibiae that had been stored for twenty-four hours had 19.1 +/- 1.5 picograms of endothelin-1 per milliliter, nearly twice that produced in the tibiae that had been stored for eight hours. Injection of acetylcholine demonstrated muscarinic receptor-mediated vasodilation in the tibiae that had been stored for four hours. In contrast, the tibiae that had been stored for eight and twenty-four hours had no evidence of acetylcholine-induced vasodilation of baseline perfusion vascular smooth-muscle tone. However, there was some preservation of endothelium-dependent vascular smooth-muscle relaxation in the tibiae that had been stored for eight and twenty-four hours, as norepinephrine-induced vascular smooth-muscle contraction was significantly greater in the presence of N(G)-monomethyl-L-arginine acetate (p < 0.05). Moreover, in the second phase of the study, a bolus injection of calcium ionophore A23187 in tibiae that had been stored for twenty-four hours relaxed vascular smooth muscle. Adrenomedullin, a novel peptide with known vasodilator properties, relaxed vascular smooth muscle in all three groups and also attenuated the pressor response to norepinephrine. In conclusion, the function of the vascular endothelium was impaired after storage at room temperature for four hours. However, the vascular endothelium in the tibiae that had been stored for twenty-four hours maintained some function with regard to the production of nitric oxide. The effect of adrenomedullin as a potent vasodilator was observed in the tibiae that had been stored for four, eight, and twenty-four hours.

Effect of Decreased Ocular Perfusion Pressure on Blood Flow and the Flicker-Induced Flow Response in the Cat Optic Nerve Head

The effect of decreased ocular mean perfusion pressure (PPm), defined as mean arterial blood pressure minus intraocular pressure (IOP), on optic nerve head blood flow (Fonh) and on the response of this flow (RFonh) to diffuse luminance flicker was investigated in 19 anesthetized cats using laser Doppler flowmetry. PPmwas decreased by increasing the IOP. The flicker stimulus consisted of 20-msec flashes delivered at 10 Hz for 30–60 sec. It illuminated a 30° diameter area of the fundus, centered at the optic disk. Decreasing PPmby 10–35% from its resting value resulted in a 23% increase in RFonh(supranormal RFonh). With further decreases in PPm, RFonhdecreased, reaching zero at a PPmbelow 20 mmHg. Fonhremained constant until PPmwas <40 mmHg and then decreased thereafter. When PPmwas brought back to resting value after having been decreased for ≈45 min, Fonhfirst increased by ≈380% and then returned to its value at rest within ≈4.5 min. At low PPm, hyperoxia decreased Fonhby 23% and restored the attenuated RFonhback to the value at resting PPmand hypoxia did not increase Fonh, as it did at normal PPm. This study confirms that the optic nerve head circulation is autoregulated over a wide range of PPmand reveals, for the first time, a hyperemic response to a prolonged decrease in PPm. It suggests that hypoxia plays a role in abolishing RFonhat low PPmand that the supranormal RFonhat moderately decreased PPmis due to an increase in the flicker-induced ganglion cell activity.

Pulse pressure-related changes in coronary flow in vivo are modulated by nitric oxide and adenosine.

Acute increases in arterial pulsatile load imposed on the left ventricle can increase coronary flow without commensurate changes in myocardial oxygen consumption. One explanation is that augmenting pulsatile perfusion at the same mean pressure itself stimulates flow by releasing endothelium-mediated vasorelaxant factors such as NO. The present study tested this hypothesis and determined whether NO and adenosine modulate this response. In open-chest anesthetized dogs, the distal left anterior descending coronary artery (LAD) was whole-blood-perfused by a novel servopump system to control mean and pulsatile perfusion pressure within the isolated vascular bed. Central aortic pressure was measured, stored to computer memory, and then digitally modified (varying the pulse pressure [PP]) to generate a real-time servocommand that was still synchronous with ventricular contraction. Left heart workload was unchanged. LAD flow was measured before and after increasing the PP (to 60 to 100 mm Hg) from baselines of either 0 or 40 mm Hg. With normal basal coronary vascular tone, raising the PP increased flow (+9 +/- 2% at a PP of 100 mm Hg). This response was markedly amplified (+39 +/- 8%) when basal tone was first partially reduced by adenosine. Competitive inhibition of NO synthase by N omega-monomethyl-L-arginine reduced acetylcholine and PP-dependent flow responses by 50%. Thus, enhanced pulsatile perfusion increases in vivo coronary flow in part by triggering NO release. The marked augmentation of the PP response with reduced basal coronary tone from adenosine suggests that this mechanism may play a role in improving myocardial perfusion during exercise.

ROLE OF PROSTAGLANDINS IN HUMAN EXERCISE HYPEREMIA 1049

The time course of change in mean blood velocity (MBV; pulsed Doppler), brachial artery diameter (D; echo Doppler), shear rate(γ=8*MBV/D), blood flow (Q), and mean perfusion pressure (MPP; finapres) were assessed to investigate the singular role that prostaglandins(PG) have on vascular dynamics during submaximal voluntary exercise in humans. 8 healthy men performed 5 min of supine dynamic handgrip exercise by alternately raising and lowering a weight (≈ 10% maximal voluntary contraction) with a work/rest cycle of 1s/1s. γ and ˙Q dynamics were altered by performing the exercise with the arm held 50° Above or Below the heart. Ibuprofen (IBU) (1200 mg/d), to reduce PG production, and placebo(PLAC), were administered orally for 2 d prior to two separate, and randomly assigned, testing sessions. Resting heart rate was reduced with IBU(52.2±2.6) compared with PLAC (56.6±2.9) (P<0.05) without change to MPP suggesting peripheral vasoconstriction had occurred. With IBU, end exercise MBV (31.6±1.7 cm/s) and D (4.7±0.1 mm) were modestly, but not significantly (P>0.05), altered compared with PLAC(35.0±2.7 cm/s, and 4.5±0.2 mm; MBV, and D respectively) but only in the Below tests after ≈ 15s of exercise. During Below tests, exercise γ was not different between IBU (52.8±3.4 s-1) and PLAC (52.7±5.7 s-1). Although it had been hypothesized that IBU would inhibit a PG-mediated vasodilation and reduce exercise hyperemia, the data indicate that either 1) IBU was not effective, 2) is of limited importance, or 3) that compensatory mechanisms allow a near normal response.

Adverse influence of systemic vascular stiffening on cardiac dysfunction and adaptation to acute coronary occlusion.

[corrected] Age is an independent risk factor for increased mortality from ischemic heart disease. Arterial stiffening with widening of the pulse pressure may contribute to this risk by exacerbating cardiac dysfunction after total coronary artery occlusion. To test the above hypothesis, 14 open-chest dogs underwent surgery in which the intrathoracic aorta was bypassed with a stiff plastic tube. Directing ventricular outflow through the bypass widened the arterial pulse pressure from 41 to 115 mm Hg at similar mean pressure and flow. Hearts ejecting into the native aorta (NA) exhibited only modest dysfunction after two minutes of mid-left anterior descending coronary artery occlusion. However, the same occlusion applied during ejection into the bypass tube (BT) induced far more severe cardiodepression (ie, systolic pressure fell by -41+/-10 mm Hg for BT versus -15+/-3 mm Hg for NA, and end-systolic volume rose by 15+/-3 versus 6+/-2 mL), with a threefold greater decline in ejection fraction. This disparity was not due to higher baseline work loads because total pressure-volume area was similar in both cases. Furthermore, marked increases in basal work load and wall stress induced by angiotensin II infusion (in four additional studies) did not reproduce this behavior. Although peak systolic chamber stress was greater with the BT, this did not increase systolic dyskinesis as measured in the central ischemic zone. However, the total mass of myocardium that was rendered severely ischemic (ie, flow reduced by > or = 80%) was twice as large with BT ejection, likely expanding the region of dyskinesis. This disparity may relate to altered phasic coronary flow during BT ejection, which displays marked enhancement of systolic flow and renders the heart more vulnerable to diminished mean and systolic perfusion pressures. Cardiac ejection into a stiff systemic vasculature augments cardiac dysfunction and ischemia due to coronary occlusion by tightening the link between cardiac systolic performance and myocardial perfusion. This may contribute to the higher mortality risk from ischemic heart disease due to age.

Minimal role of nitric oxide in basal coronary flow regulation and cardiac energetics of blood-perfused isolated canine heart.

1. The role of nitric oxide (NO) in the regulation of basal coronary perfusion and ventricular chamber energetics was studied in isovolumetrically contracting isolated blood-perfused canine hearts. Hearts were cross-perfused by a donor animal prior to isolation, and chamber volume controlled by a servo-pump. Coronary sinus flow and arterial-coronary sinus oxygen difference were measured to determine energetic efficiency. 2. NO synthase (NOS) was competitively inhibited by NG-monomethyl-L-arginine (L-NMMA; 0.5 mg kg-1, intracoronary), resulting in a reduction of acetylcholine (50 micrograms min-1)-induced flow augmentation from 143 to 62% (P < 0.001). 3. NOS inhibition had no significant effect on basal coronary flow. Coronary pressure-flow relationships were determined at a constant cardiac workload by varying mean perfusion pressure between 20 and 150 mmHg. Neither the shape of the relationship, nor the low-pressure value at which flow regulation was substantially diminished were altered by NOS inhibition. 4. Myocardial efficiency was assessed by the relationship between myocardial oxygen consumption and total pressure-volume area (PVA), with cavity volume altered to generate varying PVAs. This relative load-independent measure of energetic efficiency was minimally altered by NOS inhibition. 5. These results contrast with isolated crystalloid-perfused heart experiments and suggest that in hearts with highly controlled ventricular loading and whole-blood perfusion, effects of basal NO production on coronary perfusion and left ventricular energetics are minimal.

Urinary bladder distension: its effects on carotid baroreceptor reflex left ventricular inotropic response in the dog.

1. The effects of distension of the urinary bladder on heart rate, maximum rate of change of left ventricular pressure (dP/dt max) and hindlimb vascular resistance together with their modulation at different carotid sinus pressures were studied in dogs anaesthetized with a mixture of chloralose and urethane and artificially ventilated. 2. When the carotid sinus mean perfusion pressure was raised in randomly selected steps from 60 to 210 mmHg, it caused a progressive bradycardia, and a reduction in left ventricular dP/dt max and in arterial blood pressure, together with vasodilatation in the perfused hindlimb. Distension of the bladder at each level of carotid sinus pressure resulted in tachycardia, a small but significant increase in left ventricular dP/dt max (160 +/- 30 mmHg s-1) and hindlimb vasoconstriction. 3. When heart rate and arterial blood pressure were held constant to exclude these secondary effects on left ventricular dP/dt max, raising the carotid sinus pressure caused a progressive reduction in left ventricular dP/dt max and hindlimb vasodilatation. Superimposition of tests of bladder distension at each level of sinus pressure resulted in variable responses, but overall there was a significant increase in left ventricular dP/dt max of 190 +/- 54 mmHg s-1. Hindlimb vasocontriction, however, was a consistent finding. 4. The gain of the relationship between the carotid sinus perfusion pressure and left ventricular dP/dt max was unaffected by distension of the bladder. 5. It is concluded that, when changes secondary to increases in heart rate and blood pressure are prevented, distension of the bladder causes a small but significant reflex increase in left ventricular dP/dt max. The responses, however, are variable and the possible reasons for this are discussed.

Effect of substrate manipulation on reducing ischemia/reperfusion injury in isolated perfused rat hearts

The objective of this investigation was to assess the effect of substrate manipulationon reducing ischemia/reperfusion injury (IRI). Isolated rat hearts were perfused with modified Krebs-Henseleit buffer containing either (in mM): glucose 11 (G1), glucose 22 (G2), or glucose 11 with either xylitol 11 (GX), mannitol 11 (GM), L-leucine 1 (GL), or L-glutamic acid 2 (GGA), respectively. Hearts were subjected to 10 min of global no-flow ischemia, followed by 20 min of reperfusion. Mean tissue perfusion, oxygen consumption, and peak left ventricular pressure (PLVP) were determined at baseline, in the first minute of regular heart rhythm following ischemia, and after 20 minutes of reperfusion. Reperfusion arrhythmia (in sec) was significantly (all p < 0.05) shorter in GGA (115 ± 33) vs G1 (315 ± 29) and G2 (273 ± 33), and also in GL (161 ± 26) vs G1. Dry/wet heart weight ratios were also greater in GGA (0.20), when compared with G2 (0.16), GX (0.17), GM (0.17), GM (0.17), and GL (0.17) (all p < 0.02), suggesting less cellular/interstitial edema. Percent recovery in PLVP was improved (p < 0.03) in GL (81 ± 2) and GGA (81 ± 2) vs. G2 (71 ± 3), without significant alterations in oxygen consumption. Thus, cardiac IRI can be diminished by substrate manipulation, especially by augmentation of glutamate and leucine, most likely due to an improved anaerobic energy generation and utilization.

Noninvasive Monitoring of Cerebral Perfusion by Transcranial Doppler During Fulminant Hepatic Failure and Liver Transplantation

Noninvasive Monitoring of Cerebral Perfusion by Transcranial Doppler During Fulminant Hepatic Failure and Liver Transplantation

Noninvasive Monitoring of Cerebral Perfusion by Transcranial Doppler During Fulminant Hepatic Failure and Liver Transplantation

Survival in patients with fulminant hepatic failure (FHF) treated medically, rather than surgically, ranges from 12%-67% (mean 39%), depending on the cause of the disease (1). The major cause of mortality is increased intracranial pressure (ICI’) from brain edema (2). For patients with a poor prognosis (3), orthotopic liver transplantation may be the definitive treatment (41, even though, only a few years ago, some considered this treatment ineffective by the time patients reached Grade 4 encephalopathy (5). ICI’ monitoring allows physicians to use specific therapy to control intracranial hypertension. Continuous measurement of ICI’ perioperatively in the management of FHF has been associated with a survival rate of 54%74% in a series of six to 23 patients (6-9), which is generally higher than with medical means (l), and was as high as 92% for the selected group who had undergone liver transplantation (6). Such invasive monitoring, however, is especially risky in FHF patients with coagulopathy, in whom the incidence of bleeding from ICI’ monitoring ranges from 5%-22% (6,8) with a mortality rate of 60% (6). Although the use of ICI’ monitoring for FHF has become more routine (8), not all centers support the use of this invasive monitoring. We describe a patient with FHF and brain edema who underwent liver transplantation and whose cerebral perfusion was monitored noninvasively by transcranial Doppler (TCD) imaging, as well as invasively by ICI’. The noninvasive technique provided adequate information when cerebral perfusion was low, comparable with the invasive technique, and allowed intracranial hypertension to be diagnosed and treated effectively.

Experimental study of cerebral autoregulation during cardiopulmonary bypass with or without pulsatile perfusion

Twenty-four adult mongrel dogs were divided into four equal groups according to the following method of cardiopulmonary bypass: normothermic continuous (so-called nonpulsatile) perfusion, normothermic pulsatile perfusion, hypothermic continuous perfusion, and hypothermic pulsatile perfusion. Cerebral blood flow was determined by measuring the volume of sagittal sinus venous blood outflow with a transit-time ultrasonic flowmeter. Cardiopulmonary bypass was initiated at a flow rate of 80 ml/kg per minute. Cerebral temperature was maintained at 37 degrees C in the normothermic groups and at 25 degrees C in the hypothermic groups. Arterial pH and carbon dioxide were maintained within the physiologic range by alpha-stat acid-base regulation. Mean cerebral perfusion pressure and blood flow were not affected during 90 minutes of the bypass. The respective values were 67.1 mm Hg and 37.1 ml/100 gm brain per minute with normothermic continuous perfusion, 72.8 mm Hg and 39.0 ml/100 gm per minute with nonpulsatile perfusion, 98.0 mm Hg and 23.0 ml/gm per minute with hypothermic continuous perfusion, and 86.8 mm Hg and 22.3 ml/100 gm per minute with hypothermic pulsatile perfusion. Pump flow rates were altered from 10 to 120 ml/kg per minute in a stepwise fashion to obtain graded changes of perfusion pressure. Cerebral blood flow, however, was not changed significantly by cerebral perfusion pressure so long as perfusion pressure was greater than 50 mm Hg. Conversely, cerebral blood flow changed proportionally with cerebral perfusion pressure at a pressure less than 50 mm Hg. The correlation between cerebral blood flow and perfusion pressure was described as two separate lines determined by linear regression. The slope of the regression line relating cerebral blood flow to perfusion pressure was 0.16 +/- 0.08 for a cerebral perfusion pressure above 50 mm Hg and 0.68 +/- 0.11 below 50 mm Hg in the normothermic continuous perfusion group; 0.14 +/- 0.09 and 0.32 +/- 0.09 with normothermic pulsatile perfusion; 0.10 +/- 0.04 and 0.62 +/- 0.18 with hypothermic continuous perfusion; 0.09 +/- 0.08 and 0.39 +/- 0.04 in the hypothermic pulsatile perfusion group. The slope above 50 mm Hg was significantly smaller and closer to zero in all groups than it was at a perfusion pressure below 50 mm Hg (p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Optimal perfusion pressure for experimental retrograde cerebral perfusion.

We evaluated cerebral metabolism during retrograde cerebral perfusion (RCP) and circulatory arrest during profound hypothermia, and also investigated the effects of perfusion pressure on RCP. Twenty-four adult mongrel dogs were placed on cardiopulmonary bypass and cooled to a nasopharyngeal temperature of 20 degrees C. At this temperature, hypothermic circulatory arrest (HCA; n = 6), and RCP with a perfusion pressure of 10 mmHg (RCP10; n = 6), 20 mmHg (RCP20; n = 6), and 30 mmHg (RCP30; n = 6) were carried out for 60 minutes. RCP was performed with oxygenated blood via the bilateral maxillary veins, and the retrograde flow rate was regulated to maintain a mean perfusion pressure of 10, 20, or 30 mmHg in the external jugular vein. At 60 minutes of RCP, we measured nasopharyngeal temperature; regional cerebral blood flow (rCBF); cerebral oxygen consumption, carbon dioxide excretion, and excess lactate; cerebral tissue adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and energy charge; and cerebral tissue water content. In the RCP10 group, there was excess cerebral lactate, and ATP and energy charge were low. In the RCP30 group, the water content of cerebral tissue was significantly higher than in other groups. In the RCP20 group, temperature was maintained in a narrow range, oxygen consumption and carbon dioxide excretion could be observed, there was no excess lactate, and ATP and energy charge were significantly higher than in the HCA group. In conclusion, RCP can provide adequate metabolic support for the brain during circulatory arrest, and a perfusion pressure of 20 mmHg is most appropriate for RCP.