Vasodilator responses to desmopressin and its diluent, chlorobutanol, in the hindquarters vascular bed of the cat

Desmopressin is a synthetic analog of vasopressin used to promote hemostasis and reduce postoperative blood loss. Recent studies have shown that desmopressin decreases arterial blood pressure in the anesthetized rat and relaxes isolated segments of aorta and pulmonary artery. Responses to a clinical preparation of desmopressin were investigated in the hindquarters vascular bed of the cat under constant flow conditions so that changes in perfusion pressure directly reflect changes in vascular resistance. Responses to desmopressin and its vehicle, and the effect of receptor antagonists, inhibitors of prostaglandin, and nitric oxide synthesis inhibitors, were investigated.     

Perfusion of ischemic myocardium during anesthesia with sevoflurane

BACKGROUND: Sevoflurane produces direct vasodilation of coronary arteries in vitro and decreases coronary vascular resistance in vivo, pharmacologic properties that may contribute to the development of "coronary steal." This investigation examined the effects of sevoflurane on the distribution of regional myocardial perfusion in chronically instrumented dogs with steal-prone coronary artery anatomy. METHODS: Dogs were chronically instrumented for measurement of aortic and left ventricular pressure, diastolic coronary blood flow velocity and subendocardial segment length. After recovery from surgery, dogs underwent repetitive, brief, left anterior descending coronary artery (LAD) occlusions via an implanted hydraulic vascular occluder to enhance collateral development. A progressive left circumflex coronary artery (LCCA) stenosis was also obtained using an ameroid constrictor. After development of LCCA stenosis, the LAD was totally occluded to produce a model of multivessel coronary artery disease. Systemic hemodynamics, regional contractile function and myocardial perfusion measured with radioactive microspheres were assessed in the conscious state and during sevoflurane anesthesia at 1.0 and 1.5 MAC with and without restoration of arterial blood pressure and heart rate to conscious levels. RESULTS: Total LAD occlusion with simultaneous LCCA stenosis increased heart rate, mean arterial pressure, left ventricular systolic and end-diastolic pressures, end-diastolic segment length, and rate-pressure product in conscious dogs. Subsequent administration of sevoflurane caused dose-related decreases in arterial pressure, left ventricular systolic pressure, double product, and peak rate of increase of left ventricular pressure at 50 mmHg. Perfusion of normal myocardium was unchanged during sevoflurane anesthesia. In contrast, sevoflurane caused dose-dependent decreases in blood flow to myocardium supplied by the stenotic LCCA, which returned to control levels after restoration of heart rate and arterial pressure. No reduction in collaterally derived blood flow to the occluded region was produced by 1.0 or 1.5 MAC sevoflurane. No redistribution of blood flow away from the occluded LAD region to normal or stenotic myocardium occurred during sevoflurane anesthesia. In fact, increases in the ratio of blood flow between occluded and normal zones or occluded and stenotic zones were observed in the subepicardium during 1.5 MAC sevoflurane with maintenance of the heart rate and arterial pressure at conscious levels. CONCLUSIONS: The results demonstrate that sevoflurane does not reduce or abnormally redistribute myocardial blood flow derived from coronary collateral vessels in a chronically instrumented canine model of multivessel coronary artery obstruction.     

Beat-to-beat modulation of heart rate is coupled to coronary perfusion pressure in the isolated heart

A goal of clinicians caring for heart transplant recipients has been to use heart rate variability as a noninvasive means of diagnosing graft rejection. The determinants of beat-to-beat variability in the surgically denervated heart have yet to be elucidated. We used an isolated, blood buffer-perfused porcine heart preparation to quantitatively assess the relationship between coronary perfusion and sinus node automaticity. Hearts (n = 9) were suspended in a Langendorff preparation, and heart rate (HR) fluctuations were quantified while perfusion pressure was modulated between 70/50, 80/60, 90/70, and 100/80 mmHg at 0.067 Hz. In 32 of 32 recordings, the cross spectrum of perfusion pressure vs. HR showed the largest peak centered at 0.067 Hz. In eight of nine experiments during nonpulsatile perfusion, HR accelerated as perfusion pressure was increased from 40 to 110 mmHg (mean increase 24.2 +/- 3.0 beats/min). HR increased 0.34 beats/min per mmHg increase in perfusion pressure (least squares linear regression y = -25.8 mmHg + 0.34x; r = 0.88, P < 0.0001). Administration of low- and high-dose nitroglycerin (Ntg) resulted in a modest increase in flow but produced a significant decrease in HR and blunted the response of HR to changes in perfusion pressure (HR increase 0.26 beats. min-1. mmHg-1, r = 0.87, P < 0.0001 after low-dose Ntg; 0.25 beats. min-1. mmHg-1, r = 0.78, P < 0.0001 after high-dose Ntg). These experiments suggest that sinus node discharge in the isolated perfused heart is mechanically coupled to perfusion pressure on a beat-to-beat basis.     

Effect of carperitide (alpha-human atrial natriuretic polypeptide) on the cardiovascular system in experimental animals

The cardiovascular and diuretic actions of carperitide were studied in experimental animals. Carperitide relaxed various canine arteries and veins that were contracted by high K+ or norepinephrine. Carperitide stimulated particulate guanylate cyclase from rat thoracic aortas. Carperitide had almost no effect on coronary perfusion pressure or heart rate, but caused a slight decrease in contractile force in isolated guinea pig hearts. Carperitide tended to decrease isoproterenol-induced renin release from isolated rat kidney slices and elicited decreases in angiotensin II-induced aldosterone release from bovine zona glomerulosa cells. Intravenous injection of carperitide elicited decreases in arterial blood pressure and total peripheral resistance in the anesthetized and conscious dogs. Carperitide also elicited transient increases in cardiac output and coronary blood flow followed by slight decreases in them. Intravenous infusion of carperitide elicited decreases in pulmonary capillary wedge pressure, pulmonary pressure and right atrial pressure in association with elevating plasma carperitide (ANP like immuno-reactivity) level in dogs with heart failure induced by coronary artery occlusion and saline loading. These results suggest that carperitide decreases both preload and afterload and can improve the untoward hemodynamic alterations in animals with acute experimental heart failure.     

Ocular and regional cerebral blood flow in aging Fischer-344 rats

Vascular remodeling and changes in vascular responsiveness occur in the rat cerebrum with old age. This includes reductions in cerebral arteriolar numerical density, cross-sectional area, distensibility, the relative proportion of distensible elements in the cerebral arteriolar wall, and reduced endothelium-dependent relaxation. The purpose of this study was to test the hypothesis that old age results in an increase in vascular resistance and, correspondingly, a decrease in blood flow to ocular, regional cerebral, and spinal tissue in the rat. Blood flow was measured in the eye, olfactory bulb, left and right cerebrum, pituitary gland, midbrain, pons, cerebellum, medulla, and spinal cord of juvenile (2-mo-old, n = 6), adult (6-mo-old, n = 7), and aged (24-mo-old, n = 7) male Fischer-344 rats. Arterial pressure and blood flow were used to calculate vascular resistance. Vascular resistance in the eye of aged rats (6.03 +/- 1.08 mmHg . ml-1 . min . 100 g) was higher than that in juvenile (3.83 +/- 0.38 mmHg . ml-1 . min . 100 g) and adult rats (3.12 +/- 0.24 mmHg . ml-1 . min . 100 g). Similarly, resistance in the pons of older rats (2.24 +/- 0.55 mmHg . ml-1 . min . 100 g) was greater than in juvenile (0.66 +/- 0.06 mmHg .ml-1 . min . 100 g) and adult rats (0.80 +/- 0.11 mmHg . ml-1 . min . 100 g). In contrast, vascular resistance in the pituitary gland was lower in the aged rats (juvenile, 3.09 +/- 0.22; adult, 2.79 +/- 0.42; aged, 1.73 +/- 0.32 mmHg . ml-1 . min . 100 g, respectively). Vascular resistance was not different in other cerebral tissues or in the spinal cord in the aged rats. These data suggest that regional cerebral and spinal blood flow and vascular resistance remain largely unchanged in conscious aged rats at rest but that elevations in ocular vascular resistance and, correspondingly, decreases in ocular perfusion with advanced age could have serious adverse effects on visual function.     

Vessel size, antioxidants, and restenosis: never too small, not too little, but often too late

BACKGROUND: Diagnostic laparoscopy has been used in abdominal trauma patients, although its role is not well defined. The safety of laparoscopic evaluation in trauma patients with severe intraabdominal hemorrhage has not yet been analyzed. The purpose of this study is to evaluate the hemodynamic and metabolic effects of CO2 pneumoperitoneum (COI) in hemorrhaged animals through a retroperitoneal hematoma (RH). METHODS: Twenty-two 15-20-kg mongrel dogs were monitored for systemic and pulmonary hemodynamics, inferior vena cava pressure, and arterial blood gases. After 1 h of baseline, all animals were submitted to a RH. After 45 min the dogs were randomized into two groups. Control (CTR): dogs were submitted only to a RH; pneumoperitoneum (PN): dogs were submitted to a RH and 45 min later they were insufflated to an intraabdominal pressure of 10 mmHg with medical-grade CO2 gas for 30 min. Echocardiography was performed, only in PN animals, at baseline, 45 and 60 min after RH. RESULTS: RH induced a shock condition with low, sustained levels of arterial pressure, cardiac index, left ventricular stroke index, base excess, and oxygen delivery which were further depressed following COI. Three deaths occurred in the PN group, all of them toward the end of COI. During COI, hypercapnia was observed in one animal. COI did not impair systolic function or ejection fraction. CONCLUSIONS: COI with an IAP of 10 mmHg may be deleterious in animals with hemorrhagic shock due to an intraabdominal lesion. These findings could be clinically significant in abdominal trauma patients.     

Electrical activation of the expiratory muscles to restore cough

Many patients with spinal cord injury have paralysis of their expiratory muscles and, consequently, lack an effective cough. The purpose of the present study was to evaluate the utility of lower thoracic spinal cord stimulation (SCS) to activate the expiratory muscles. Studies were performed on 15 anesthetized dogs. A quadripolar stimulating electrode (Medtronic Model 3586) was inserted epidurally and on the ventral surface of the lower thoracic spinal cord. Changes in airway pressure, airflow, and internal intercostal and abdominal muscle length were monitored to assess the effects of electrical stimulation. Spinal stimulation applied at the T9-T10 spinal level provided maximal changes in airway pressure generation in preliminary experiments. All subsequent studies were therefore performed with the electrode positioned at this level. The expiratory muscles were stimulated supramaximally over a wide range of lung volumes which were expressed as the corresponding change in airway pressure. The pressure-generating capacity of the expiratory muscles was evaluated by the change in airway pressure produced by SCS during airway occlusion. Peak expiratory airflow was also monitored following release of occlusion. At FRC, deflation (-10 cm H2O) and inflation (+ 30 cm H2O), SCS resulted in positive airway pressures of 44 cm H2O +/- 4 SE, 28 cm H2O +/- 3 SE, and 82 cm H2O +/- 7 SE. The relationship between airway pressure expiratory airflow generation and lung volume was linear (slope = 1.34 +/- 0.04) over the entire vital capacity range. Our results indicate that: (1) a major portion of the expiratory muscles can be activated reproducibly and in concert by electrical stimulation, and (2) this technique may be a clinically useful method of restoring cough in spinal cord injured patients.     

Strategies to prevent neurologic deficit based on motor-evoked potentials in type I and II thoracoabdominal aortic aneurysm repair

PURPOSE: Motor-evoked potentials (MEPs) were monitored during thoracoabdominal aortic aneurysm (TAAA) repair to assess spinal cord ischemia and evaluate the subsequent protective strategies to prevent neurologic deficit. METHODS: Between January 1996 and December 1997, 52 consecutive patients with type I (n = 24) and type II (n = 28) TAAA underwent surgery (mean patient age, 60 years; range, 21-78 years). The surgical protocol included left heart bypass, cerebrospinal fluid drainage, and monitoring transcranial myogenic MEPs. When spinal cord ischemia was detected, distal aortic pressure and mean arterial pressure were increased. By means of sequential crossclamping, MEPs were used to identify critical intercostal or lumbar arteries. RESULTS: Reproducible MEPs could be recorded in all patients, and spinal cord ischemia was detected within 2 minutes. During distal aortic perfusion, 14 patients (27%) showed rapid decrease in the amplitude of MEPs to less than 25% of baseline, indicating spinal cord ischemia, which could be corrected by increasing distal aortic pressure. The mean distal aortic pressure to maintain adequate cord perfusion was 66 mm Hg; however, it varied among individuals between 48 and 110 mm Hg. In 24 patients (46%), MEPs disappeared after segmental clamping and returned after reattachment of intercostal arteries. In 9 patients (17%), MEPs disappeared completely, but no intercostal arteries were found. After aortic endarterectomy, 6 or 8 mm Dacron grafts were anastomosed to intercostal arteries, and MEPs returned after reperfusion. Using this aggressive surgical approach based on MEPs, no early or late paraplegia occurred in this series. CONCLUSION: Monitoring of MEPs is an effective technique to assess spinal cord ischemia. Operative strategies based on MEPs prevented neurologic deficits in patients treated for type I and II TAAA.     

Pathways regulating cardiovascular changes during volume loading in awake dogs

The role played by the cardiac sympathetic nerves and arterial baroreceptors in the cardiovascular responses to acute volume loading was studied in conscious dogs. In 15 normally innervated animals, mean arterial pressure rose 10 mmHg, heart rate increased 38 beats/min and cardiac output 1,696 ml/min, while peripheral resistance decreased 0.99 PRU. Neither bilateral baroreceptor denervation, dorsal root sections (T1-T5) or surgical interruption of the left ansa subclavia altered the above responses to acute volume loading. Bilateral section of the ansa subclavia (total cardiac sympathectomy) significantly reduced the heart rate response from 35 +/- 5 to 20 +/- 5 beats/min but did not alter other changes. A similar reduction in heart rate response was observed following selective section of the right ansa subclavia. Intravenous infusions of epinephrine augmented the heart rate response in both normally innervated and cardiac sympathectomized dogs. It is suggested that although the primary efferent pathway for the reflex trachycardia is via the vagus, responses are modulated by sympathetic neural activity. Additionally, the nervous system was not shown to play a measureable role in the observed peripheral resistance changes.     

Intraoperative monitoring of the motor pathway using transtracheal stimulation of the cervical spine in dogs

Although SEP monitoring of the spinal cord has been a well established method recently, not an ultimate, perfectly developed technique for monitoring of the motor system is known so far, particularly, because of the disturbing effect of narcotic drugs and relaxants on the motor evoked potentials. In this study the upper part of the spinal cord was stimulated in 14 anesthetized and relaxed dogs with a cathode attached to the intratracheal tube and an anode fixed to the cervical spinous processes. Single and serial stimuli were applied. Recordings were obtained from the exposed right femoral nerve and quadriceps muscle. Averaging was necessary when using serial stimulations. Responses were consequent and reproducible during regular anesthesia. The origin of the different responses in the spinal cord is discussed. The method seems to be appropriate for intraoperative monitoring of the thoracolumbar spine.     

Studies on the viability of the isolated vascularly perfused rat colon

The colon contains large numbers of endocrine cells. Insight into their physiological function is limited. This is due to the fact that no sufficient model of isolated endocrine colon cells is available. In the present study we introduce an isolated vascularly perfused colon model for in vitro studies. This model offers the advantage that it keeps the endocrine cells in their physiological orientation and environment. The gut mucosa is highly sensitive to ischemia. Therefore, a careful validation of its viability is crucial in gut organ preparations. This study demonstrates that, by utilizing an oxygenated vascular medium supplemented with 25% washed bovine erythrocytes, a perfusion of the colon is achieved for at least 1 h without obvious tissue injuries. During this time parameters such as perfusion pressure, venous lactate dehydrogenase release, glucose consumption, lactate output, oxygen consumption, perfusate loss by the preparation and morphology were analyzed. Dependent on stimulation, the endocrine L cells of the colon released glucagon-like peptide-I upon arterial perfusion of methacholine or gastrin-releasing peptide. In conclusion, a model for the isolated perfusion of the colon is introduced which is suitable for studies of endocrine colon cells.     

Renal perfusion pressure is an important determinant of sodium and calcium excretion in DOC-salt hypertension

This study tested the hypothesis that the increased renal perfusion pressure in DOC-salt hypertension is essential for the maintenance of sodium balance and is responsible for the hypercalciuria associated with this model. Twelve chronically instrumented dogs were placed on a high salt intake and mean arterial pressure (MAP) was measured 24 h/day. After a control period, a 17-day DOC infusion period was begun. In six dogs, however, renal perfusion pressure (RPP) to both kidneys was maintained at control levels for the first 12 days of the DOC infusion by the continuous, servo-controlled adjustment of a suprarenal silastic occluder on the abdominal aorta. The servo-controlled dogs had significantly more sodium retention and a greater increase in blood pressure than the six control DOC hypertensive dogs. Urinary calcium excretion in the control dogs began to increase from 24 +/- 6 mg/day on day 1 of DOC, and increased progressively to 100 +/- 14 and 175 +/- 30 mg/day by days 7 and 12, respectively. Plasma ionized calcium decreased, and parathyroid hormone (PTH) (1-84) increased, significantly by day 4. The hypercalciuria was not different in the servo-controlled dogs for the first 7 days of DOC, but was attenuated thereafter. Thus, increased RPP is important in restoring sodium balance and in maintaining the calciuresis in DOC-salt hypertension; however, other mechanisms also are important, particularly during the onset of hypertension.     

A case report of a successful surgery for thoracoabdominal aortic aneurysm under partial cardiopulmonary bypass with selective perfusion of major abdominal branches

A 69-year-old man showed gradually developing thoracoabdominal aortic aneurysm (TAAA) after coronary artery bypass grafting. The patient underwent graft replacement of TAAA uneventfully under partial cardiopulmonary bypass with selective perfusion of major abdominal branches. The major abdominal branches and two pairs of intercostal arteries were reconstructed. The patient showed no organ failure or spinal damage postoperatively. Partial cardiopulmonary bypass with selective perfusion of abdominal branches successfully protected both the visceral organs and the spinal cord from ischemia in a TAAA surgery.     

The rate of force generation by the myocardium is not influenced by afterload

The influence of afterload on the rate of force generation by the myocardium was investigated using two types of preparations: the in situ dog heart (dP/dt) and isolated papillary muscle of rats (dT/dt). Thirteen anesthetized, mechanically ventilated and thoracotomized dogs were submitted to pharmacological autonomic blockade (3.0 mg/kg oxprenolol plus 0.5 mg/kg atropine). A reservoir connected to the left atrium permitted the control of left ventricular end-diastolic pressure (LVEDP). A mechanical constriction of the descending thoracic aorta allowed to increase the systolic pressure in two steps of 20 mmHg (conditions H1 and H2) above control values (condition C). After arterial pressure elevations (systolic pressure C: 119 +/- 8.1; H1: 142 +/- 7.9; H2: 166 +/- 7.7 mmHg; P < 0.01), there were no significant differences in heart rate (C: 125 +/- 13.9; H1: 125 +/- 13.5; H2: 123 +/- 14.1 bpm; P > 0.05) or LVEDP (C: 6.2 +/- 2.48; H1: 6.3 +/- 2.43; H2: 6.1 +/- 2.51 mmHg; P > 0.05). The values of dP/dt did not change after each elevation of arterial pressure (C: 3,068 +/- 1,057; H1: 3,112 +/- 996; H2: 3,086 +/- 980 mmHg/s; P > 0.05). In isolated rat papillary muscle, an afterload corresponding to 50% and 75% of the maximal developed tension did not alter the values of the maximum rate of tension development (100%: 78 +/- 13; 75%: 80 +/- 13; 50%: 79 +/- 11 g mm-2 s-1, P > 0.05). The results show that the rise in afterload per se does not cause changes in dP/dt or dT/dt.     

Effects of changes in intraocular pressure on human ocular haemodynamics

PURPOSE: Myogenic autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. Ocular perfusion pressure is defined as the difference between ocular arterial pressure and ocular venous pressure, the latter dependent on intraocular pressure (IOP). The aim of the present study was to investigate the effect of moderate increases in IOP on ocular haemodynamics. METHODS: Changes in IOP (+ 10 mmHg, +20 mmHg) were induced by a suction cup in 10 healthy subjects. Ocular fundus pulsations in the macula and the optic disc were measured by laser interferometry; blood flow velocities in the central retinal artery (CRA) and in the ophthalmic artery (OA) were measured by Doppler sonography. RESULTS: Changes in IOP caused a significant reduction in fundus pulsations, which was more pronounced in the macula (at +10 mmHg: -9 +/- 2%, p < 0.01; at +20 mmHg: -19 +/- 3%, p < 0.001) than in the optic disc (at +10 mmHg: -5 +/- 2% (ns); at +20 mmHg: -9 +/- 3%, p < 0.01). Mean flow velocity in the CRA was reduced by -5 +/- 3% at +10 mmHg (ns) and by -14 +/- 5% at +20 mmHg (p < 0.005), resistive index was increased by +4 +/- 1% at +10 mmHg (p < 0.05) and by +6 +/- 2% at +20 mmHg (p < 0.01). In contrast, a rise in IOP did not affect blood flow parameters in the OA. CONCLUSIONS: Our results from fundus pulsation measurements indicate that choroidal blood flow decreases when IOP is increased. The Doppler sonographic findings in the CRA indicate reduced blood flow velocity in this artery during raised IOP.     

Low-dose midazolam attenuates predatory odor avoidance in rats

Based on the premise that optimal drug delivery might improve the efficacy of locoregional treatment for solid tumors, the authors set up an experimental model for isolation perfusion in surgical specimens from patients resected for carcinoma of the colon. Ten surgical specimens were cannulated, washed internally and externally with saline solution, promptly cooled to 4 degreesC, connected to a circuit, and perfused with Krebs-Henselait modified solution, concentrated red blood cells, albumin, desamethasone, glucose, and heparin for 60 minutes at a target temperature of 37 degreesC. Organ temperature, flow rate, perfusion pressure, and metabolic and functional parameters were checked at 5, 20, and 60 minutes of perfusion. A paraphysiologic perfusion procedure was achieved. Mean values (and ranges) were as follows: temperature 37 degreesC (35. 1-39.6 degreesC); flow rate 10.2 (5.6-17.9) ml/min/100 g; arterial pressure 96 (42-154) mmHg; arterial pH 7.3 (7.1-7.5); arterial PO2 183 (78-304) mmHg; arterial PCO2 36 (31-46) mmHg. No important signs of tissue damage were found at histology. Autonomous or stimulated peristalsis (or both) was present throughout the experiment. Mean O2 extraction was 7.9 ml/min/100 g (range 3.1-11.0). Mean glucose consumption was 229 mg/100 g (range 174-252). The model worked well and appears promising, particularly for future use in various pharmacokinetic and pharmacodynamic studies of antiblastic agents.     

Intrinsic regulation of blood flow in adipose tissue

Previous studies on intact human subcutaneous tissue have shown, that blood flow remains constant during minor changes in perfusion pressure. This so-called autoregulatory response has not been demonstrable in isolated preparations of adipose tissue. In the present study on isolated, denervated subcutaneous tissue in female rabbits only 2 of 12 expts. revealed an autoregulatory response during reduction in arterial perfusion pressure. Effluent blood flow from the tissue in the control state was 15.5 ml/100 g-min (S.D. 6.4, n = 12) corresponding to slight vasodilatation of the exposed tissue. Following total ischemia all experiments showed a period with reactive hyperemia, and both duration of hyperemia and excess flow was related to the duration of the ischemia. This response therefore seems more resistant to the experimental procedure, while autoregulation of blood flow to lowered pressure is more susceptible to surgical exposure of the tissue. During elevation of arterial perfusion pressure blood flow in the isolated tissue showed a transient increase and then almost returned to the level during normotension, indicating an elevated vascular resistance. Raising of venous pressure elicited vasoconstriction with pronounced flow reduction. These two reactions may be important for local regulation of blood flow in subcutaneous tissue during orthostatic changes in arterial and venous pressure. It is concluded that the response in adipose tissue to changes in arterial pressure (autoregulation), venous pressure and total ischemia appear to be elicited by different mechanisms.     

Perfusion of the juxtapapillary retina and optic nerve head in acute ocular hypertension

Chronically elevated intraocular pressure (IOP) is often associated with glaucomatous optic nerve atrophy. Impaired blood flow may play a role in the pathogenesis of this disease. We present data concerning juxtapapillary retinal and optic nerve-head blood flow during acute increases in IOP. With the combination of a laser Doppler flowmeter and a scanning-laser system (Scanning Laser Doppler Flowmeter, SLDF; Heidelberg Engineering) the perfusion of the retina and the optic nerve head was quantified and visualized. Juxtapapillary retinal and optic nerve-head blood flow was measured simultaneously by SLDF during variations in IOP induced by a suction cup in nine healthy volunteers. The ocular pressure was increased for 2 min to IOP +15 mmHg, then to IOP +30 mmHg, and finally, to IOP +45 mmHg. Ocular perfusion pressure (PP) was calculated as the mean arterial blood pressure minus the IOP. The declines in juxtapapillary retinal flow as expressed in present per 10-mmHg IOP elevation ranged from 3.6% to 14.1% (median 7.4%). Over all measurements we found a significant linear relationship between juxtapapillary retinal blood flow and PP (r = 0.55, P < 0.0001). The observed decrease in optic nerve-head blood flow with increasing IOP was significantly greater as compared with the retinal blood flow decrease (8.4%/10 mmHg versus 7.4%/10 mmHg, P < 0.05). SLDF enables the quantification and visualization of perfused capillaries of the retina and the optic nerve head in high resolution. Acute elevations of IOP led to a decreases in juxtapapillary retinal and optic nerve-head blood flow of 7.4% and 8.4%/ 10-mmHg IOP increase, respectively.     

Effect of intrathecal nimodipine on spinal cord blood flow and evoked potentials in the normal or injured cord

A method was developed for administering intrathecal pharmacotherapy in a rat model of spinal cord injury. The effects of intrathecal administration of nimodipine on spinal cord blood flow (SCBF) and evoked potentials (EPs) were measured in the normal and injured spinal cord. It had previously been shown that systemic nimodipine caused severe hypotension after spinal cord injury. After baseline SCBF and EPs, 15 uninjured rats were blindly allocated to one of three groups: one placebo group (n = 5); and two groups with intrathecal nimodipine, 0.05 mg/kg (n = 5), or 0.2 mg/kg (n = 5). Ten other rats received a 35 g acute clip compression injury of the spinal cord for 1 minute and, were allocated to one of two groups: placebo (n = 5); and intrathecal nimodipine 0.05 mg/kg (n = 5) given 60 min after injury. In the uninjured groups, neither 0.05 nor 0.2 mg/kg of nimodipine increased SCBF during, or 30 min after, intrathecal infusion. However, the mean arterial blood pressure (MABP) decreased significantly to 69.73.1% after the infusion of 0.2 mg/kg nimodipine and did not recover by 98 min. In all three groups of uninjured rats, the amplitude of the cerebellar EP was decreased 30 min after infusion. After spinal cord injury, there were significant decreases in MABP, SCBF and EP amplitude in both placebo and treatment groups, but there was no therapeutic benefit from nimodipine. Thus, intrathecal infusion of nimodipine did not prevent the hypotension encountered with systemic administration and exerted no beneficial effect on SCBF or EPs after acute spinal cord injury.     

Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs

The present study was undertaken to determine the effects of chronic sinoaortic (baroreceptor) denervation (SAD) on the hemodynamic and sympathetic alterations that occur in the pacing-induced model of congestive heart failure. Two groups of dogs were examined: intact (n = 9) and SAD (n = 9). Both groups of dogs were studied in the control (prepace) state and each week after the initiation of ventricular pacing at 250 beats/min. After the pacemaker was turned off, hemodynamic and plasma norepinephrine levels returned toward control levels in the prepaced state and after 1 and 2 wk of pacing. However, by 3 wk all hemodynamic and norepinephrine levels remained relatively constant over the 10-min observation period with the pacemaker off. With the pacemaker off, left ventricular end-diastolic pressure went from 2.7 +/- 1.4 (SE) mmHg during the prepace state to 23.2 +/- 2.9 mmHg in the heart failure state in intact dogs (P < 0.01). Left ventricular end-diastolic pressure increased to 27.1 +/- 2.2 mmHg from a control level of 4.2 +/- 1.9 mmHg i SAD dogs (P < 0.0003). Mean arterial pressure significantly decreased in intact and SAD dogs. Resting heart rate was significantly higher in SAD dogs and increased to 135.8 +/- 8.9 beats/min in intact dogs and 136.1 +/- 6.5 beats/min in SAD dogs. There were no significant differences in the hemodynamic parameters between intact and SAD dogs after pacing. Plasma norepinephrine was significantly lower in intact than in SAD dogs before pacing (197.7 +/- 21.6 vs. 320.6 +/- 26.6 pg/ml; P < 0.005). In the heart failure state, plasma norepinephrine increased significantly in both intact (598.3 +/- 44.2 pg/ml) and SAD (644.0 +/- 64.6 pg/ml) groups. There were no differences in the severity or the magnitude of the developed heart failure state in SAD vs. intact dogs. We conclude from these date that the arterial baroreflex is not the sole mechanism for the increase in sympathetic drive in heart failure.