RESUMO
Neuropeptide-Y (NPY), a brain peptide, is located in the walls of human coronary arteries. This study assessed the effects of NPY on the coronary circulation in 40 chloralose-anesthetized, open-chest dogs. Intracoronary NPY (42 nmol over 5.2 min) caused a 39% reduction in coronary blood flow without changing heart rate or aortic pressure. To determine whether this vasoconstriction could produce ischemia, intramyocardial pH was measured in seven dogs (group I) and decreased from 7.45 +/- 0.06 to 7.37 +/- 0.06 pH units after NPY in the subendocardium (P less than 0.0002), and from 7.45 +/- 0.06 to 7.40 +/- 0.05 pH units (P less than 0.04) in the subepicardium of the infused zone. Left ventricular ejection fraction (LVEF), measured by radionuclide angiography, decreased from 0.52 +/- 0.08 to 0.42 +/- 0.12 U (n = 5, P less than 0.01) during NPY. NPY-induced vasoconstriction was also associated with ST-T wave changes on the electrocardiogram (ECG) in eight of nine other animals (group V). In another group of six dogs (group IV), the change in small vessel resistance accounted for 94% of the increase in total resistance, so that the primary vasoconstrictor effect of NPY was exerted on small coronary arteries. Thus, NPY, a peptide found in human coronary arteries, caused constriction of primarily small coronary arteries that was severe enough to produce myocardial ischemia as determined by ECG ST-T wave changes, and decreases in intramyocardial pH and LVEF in dogs.
Assuntos
Doença das Coronárias/etiologia , Vasos Coronários/análise , Neuropeptídeo Y/administração & dosagem , Vasoconstritores/administração & dosagem , Animais , Circulação Coronária/efeitos dos fármacos , Doença das Coronárias/metabolismo , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiologia , Cães , Frequência Cardíaca/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Injeções Intra-Arteriais , Volume Sistólico/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacosRESUMO
Verapamil has been shown to depress the contractility of ischemic myocardium. The present study was designed to determine whether that effect is due to an increase in ischemic injury caused by the drug or whether it might reflect a protective effect. A critical partial occlusion was effected on the left anterior descending coronary artery of 16 open chest foxhounds. A fiberoptic pH probe was implanted in the subendocardium of the ischemic zone, and coronary blood flow was reduced by 79% from a control value of 38 +/- 4 ml/min and held constant. Mean coronary perfusion pressure was decreased 48% from its control value of 90 +/- 6 mm Hg and remained constant. Eight animals were treated with intravenous verapamil, beginning 20 to 30 minutes after the onset of ischemia, in incremental doses (5, 10 and 20 micrograms/kg per min) and eight were treated with placebo. The pH of the ischemic zone increased after institution of treatment in the verapamil group (+ 0.04 +/- 0.05 pH unit) whereas it decreased in the placebo group (- 0.06 +/- 0.4 pH unit) during the first dose (p less than 0.05). Although the difference in pH between the two groups was marked at all doses (p less than 0.03) compared with control partial occlusion, verapamil caused no significant change in heart rate (+ 0.1 +/- 1 beat/min in the verapamil group versus + 0.6 +/- 4.5 beats/min in the placebo group), mean arterial pressure (- 7.5 +/- 4 versus - 4.3 +/- 3 mm Hg, respectively) or cardiac output (- 0.2 +/- 0.07 versus - 0.02 +/- 0.04 liters/min, respectively) comparing control with the first or the second dose of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Doença das Coronárias/metabolismo , Miocárdio/metabolismo , Verapamil/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Doença das Coronárias/tratamento farmacológico , Cães , Relação Dose-Resposta a Droga , Coração/efeitos dos fármacos , Bloqueio Cardíaco/induzido quimicamente , Frequência Cardíaca/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Masculino , Contração Miocárdica/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Verapamil/efeitos adversos , Verapamil/uso terapêuticoAssuntos
Arte , Expressão Facial , Interpretação Psicanalítica , Áustria , Criança , Pessoas Famosas , História do Século XIX , História Medieval , Humanos , ItáliaRESUMO
A 6-month histologic study of vitreous carbon dental implants in dogs, without occlusion, has demonstrated that vitreous carbon is well tolerated by oral tissues in both permucosal and subgingival applications. Gingival tissues heal routinely and show the same degrees of irritation adjacent to the implant as tissues adjacent to natural teeth. Alveolar bone forms within grooves in the implant surface, providing mechanical retention, and both hard and soft tissues grow into the texture in the implant surface. The resulting interlocking between tissues and the implant appears to function effectively as a bacterial seal. The newly formed bone within the implant grooves appears to become more dense with time, resulting in a layer of dense bone surrounding the implant. No foreign body responses and no inflammation were observed in tissues adjacent to this implant material, and no degradation of the vitreous carbon implants was detected. A subsequent study of the implant under occlusion in dogs is also being conducted.
Assuntos
Materiais Biocompatíveis , Carbono/farmacologia , Implantação Dentária , Processo Alveolar/ultraestrutura , Animais , Materiais Biocompatíveis/farmacologia , Reabsorção Óssea/etiologia , Reabsorção Óssea/patologia , Tecido Conjuntivo/ultraestrutura , Células do Tecido Conjuntivo , Implantação Dentária/efeitos adversos , Implantação Dentária/instrumentação , Cães , Gengiva/ultraestrutura , Gengivite/etiologia , Gengivite/patologia , Osteogênese , Propriedades de Superfície , Cicatrização/efeitos dos fármacosRESUMO
A 6-7 month histologic study of vitreous carbon endosteal implants in occlusion was conducted in dogs to determine whether the shape of the implant has adverse effects on supporting tissues. Conical vitreous carbon implants were placed in fresh, second, and third premolar extraction sites, and the sites were allowed to heal for periods of 2 to 8 weeks prior to restoration with cast gold crowns. Gingival tissues healed routinely and showed inflammatory conditions similar to tissues adjacent to teeth, and normal sulculur depths were measured. Bone formation was observed within grooves in the implant surface, providing retention and stabilization, normal bone remodeling appeared to be occurring adjacent to the implant sites. No inflammatory responses, foreign body reactions, or infections were observed. Vitreous carbon appears well suited for application as an endosteal implant material.
Assuntos
Carbono , Cerâmica , Implantação Dentária/instrumentação , Análise do Estresse Dentário , Gengiva/anatomia & histologia , Mandíbula/anatomia & histologia , Animais , Materiais Biocompatíveis , Fenômenos Biomecânicos , Coroas , Cães , OsteogêneseRESUMO
Force relaxation and permanent deformation processes in erythrocyte membrane were investigated with two techniques: micropipette aspiration of a portion of a flaccid cell, and extension of a whole cell between two micropipettes. In both experiments, at surface extension ratios less than 3:1, the extent of residual membrane deformation is negligible when the time of extension is less than several minutes. However, extensions maintained longer result in significant force relaxation and permanent deformation. The magnitude of the permanent deformation is proportional to the total time period of extension and the level of the applied force. Based on these observations, a nonlinear constitutive relation for surface deformation is postulated that serially couples a hyperelastic membrane component to a linear viscous process. In contrast with the viscous dissipation of energy as heat that occurs in rapid extension of a viscoelastic solid, or in plastic flow of a material above yield, the viscous process in this case represents dissipation produced by permanent molecular reorganization through relaxation of structural membrane components. Data from these experiments determine a characteristic time constant for force relaxation, tau, which is the ratio of a surface viscosity, eta to the elastic shear modulus, mu. Because it was found that the concentration of albumin in the cell suspension strongly mediates the rate of force relaxation, values for tau of 10.1, 40.0, 62.8, and 120.7 min are measured at albumin concentrations of 0.0, 0.01, 0.1, and 1.% by weight in grams, respectively. The surface viscosity, eta, is calculated from the product of tau and mu. For albumin concentrations of 0.0, 0.01, 0.1, and 1% by weight in grams, eta is equal to 3.6, 14.8, 25.6, and 51.9 dyn s/cm, respectively.
Assuntos
Membrana Eritrocítica/ultraestrutura , Eritrócitos/ultraestrutura , Humanos , Matemática , Métodos , Modelos BiológicosRESUMO
To assess the relationship between conjunctival pH (pHcj), arterial pH (pHa), and cardiorespiratory variables during normal and low-flow conditions, hemorrhagic hypotension was induced in eight dogs. Conjunctival pH became significantly less than control values after a hemorrhage volume of 15 mL/kg (P less than .05); mean arterial pressure (MAP) did not fall until blood loss was 20 mL/kg. There was poor correlation between pHcj and pHa, cardiac index (CI), or MAP. There was a high degree of correlation, however, between pHcj-pHa difference (delta pH) and MAP (r = -0.886), CI (r = -0.846), and tissue oxygen extraction ratio (r = .896). The results of these experiments indicate that pHcj is a sensitive monitor of peripheral tissue perfusion, and that the degree of physiologic compromise associated with hemorrhage can be determined by analysis of the difference between arterial and conjunctival pH.
Assuntos
Túnica Conjuntiva/metabolismo , Tecnologia de Fibra Óptica/instrumentação , Animais , Pressão Sanguínea , Doenças da Túnica Conjuntiva/metabolismo , Cães , Hemorragia/metabolismo , Concentração de Íons de Hidrogênio , Monitorização Fisiológica/métodos , RespiraçãoRESUMO
A miniaturized fiberoptic PCO2 probe permits direct measurement of tissue PCO2 on nonkeratinized tissue surfaces without the heating effects produced by transcutaneous PCO2 sensors. This study of anesthetized dogs compared PCO2 measured at the palpebral conjunctiva (PcjCO2) with PaCO2 and mixed venous (PVCO2) measurements during normovolemic normotension and hypovolemic hypotension. During the control period, the average PcjCO2 was 3 +/- 1 (SEM) torr greater than PaCO2 (r = 0.98) when the latter ranged from 20 to 80 torr. There was a close association (r = 0.94) between PcjCO2 and PaCO2 when the cardiac index (CI) was greater than 2.0 L/min X m2. However, as CI decreased below this value, PcjCO2 and PaCO2 were less well correlated (r = 0.69). PcjCO2 was closely associated with PVCO2 at all stages of the experiment, both above (r = 0.95) and below (r = 0.82) a CI of 2 L/min X m2. Fiberoptic conjunctival PCO2 monitoring seems promising as a noninvasive measure of physiologic status.
Assuntos
Dióxido de Carbono/análise , Tecnologia de Fibra Óptica/instrumentação , Animais , Circulação Sanguínea , Pressão Sanguínea , Túnica Conjuntiva , Cães , Hipotensão/metabolismo , Choque/metabolismo , Choque Hemorrágico/metabolismoRESUMO
OBJECTIVE: Our objective was to investigate the accuracy of a new intravascular blood gas sensor, the Paratrend 7 (P7) (Biomedical Sensors Ltd, Pfizer Hospital Products Group, High Wycombe, England) in a porcine model. METHODS: A total of 12 sensors were inserted into 10 animals under total intravenous anesthesia. Changes in blood gas chemistry were produced over a wide range by manipulating the inspired oxygen and carbon dioxide concentrations and by adjustments in minute ventilation. Blood gas samples (BGA) were taken and analyzed during periods of stability; the results obtained were compared with the readings from the intravascular sensor. RESULTS: A total of 292 blood gas samples were taken and analyzed for pHa, PaCO2, and Po2; the results were compared with the readings from the intravascular sensor. Correlation coefficients of r = 0.98 for PCO2 and r = 0.99 for PO2 were obtained. Analysis of bias and precision as mean +/- SD of the difference (P7 - BGA) gave the following results: pH bias = -0.03, precision = +/- 0.04; PCO2 bias = 0.65 mm Hg, precision = +/- 3.1 mm Hg; and PO2 bias = -6.50 mm Hg, precision = +/- 0.6 mm Hg. No problems with clot formation on the sensor were seen, and the sensors did not appear to show the "wall effect" seen with other systems. CONCLUSIONS: The results obtained were well within the requirements for a clinically useful blood gas monitoring system.
Assuntos
Gasometria/instrumentação , Monitorização Fisiológica/instrumentação , Animais , Estudos de Avaliação como Assunto , SuínosRESUMO
The relationships between stimulus parameters and perceptions in a prosthetic feedback system were measured using psychophysical methods. Electrical stimulation of the median nerve produced a monotonic relation between frequency of stimulation and the perceived magnitude of the stimulus. There were two qualitatively different perceptions of the stimulation; one for low frequencies and one for high. These two qualities fit different psychophysical continuua, kind of stimulation, and amount of stimulation.
Assuntos
Membros Artificiais , Biorretroalimentação Psicológica , Percepção , Adulto , Braço , Limiar Diferencial , Estimulação Elétrica , Eletrodos Implantados , Humanos , Masculino , Nervo Mediano/fisiologia , SensaçãoRESUMO
To evaluate potential clinical applications of a newly developed, noninvasive fiberoptic conjunctival carbon dioxide (PcjCO2) sensor designed to measure continuously tissue PCO2 in a vascular bed supplied by the internal carotid artery, we studied the effects of graded respiratory and metabolic alkalosis and acidosis on PcjCO2 in a hemodynamically stable canine model. Respiratory changes were induced by varying the frequency of ventilation and metabolic changes were induced by incremental infusions of sodium bicarbonate and hydrochloric acid. Continuous measurement of end-tidal carbon dioxide tension (PETCO2) was also performed. During respiratory alkalosis and acidosis, PcjCO2 values correlated well with PaCO2 (r = 0.96, n = 106); linear regression analysis of PcjCO2 vs. PaCO2 produced a slope of 1.01 and a y-intercept of 3.94 over a PaCO2 range of 12 to 76 torr. The mean PcjCO2-PaCO2 gradient was 4 +/- 3 (SD) torr. PETCO2 values also correlated well with PaCO2 (r = 0.91), as well as with PcjCO2 values (r = 0.91). Both PcjCO2 and PETCO2 showed a much weaker correlation with PaCO2 during metabolic alkalosis and acidosis, partly because the variation in PaCO2 was less. Moreover, the PcjCO2-PaCO2 gradient increased during the metabolic portion of the study up to a mean of 10 +/- 8 (SD) torr during metabolic acidosis, implying a build-up and/or lack of washout of CO2 from the conjunctival tissues, despite the normal physiologic range of PaCO2 values. We conclude that in a hemodynamically stable canine model, PcjCO2 and PETCO2 values correlate well with PaCO2 during pure respiratory alkalosis and acidosis; the correlation weakens significantly, however, with metabolic alterations in tissue CO2 levels.
Assuntos
Acidose Respiratória/sangue , Alcalose Respiratória/sangue , Dióxido de Carbono/análise , Túnica Conjuntiva/análise , Tecnologia de Fibra Óptica/instrumentação , Acidose Respiratória/metabolismo , Alcalose Respiratória/metabolismo , Animais , Gasometria , Modelos Animais de Doenças , Cães , Estudos de Avaliação como Assunto , Monitorização Fisiológica/métodos , Volume de Ventilação PulmonarRESUMO
BACKGROUND: We studied the effect of intracoronary administration of arginine-8-vasopressin on blood flow in nondiseased coronary arteries and determined whether this vasoconstriction was severe enough to produce ischemia in 30 dogs. METHODS AND RESULTS: In group 1 (n = 6), after vasopressin administration coronary blood flow was decreased by 41% (p less than 0.002) without changes in heart rate or aortic pressure, and left ventricular ejection fraction measured by radionuclide angiocardiography was decreased by 18% (p less than 0.0005). In group 2 (n = 6), ischemia was confirmed by measurement of transmural pH changes. Administration of vasopressin decreased subendocardial pH of the infused zone from 7.40 +/- 0.03 to 7.31 +/- 0.07 (p less than 0.01). The subendocardial pH of the zone not infused with vasopressin did not change. To overcome the intrinsic regulation of blood flow, operating primarily in small coronary arteries, we hypothesized that vasopressin must increase resistance primarily in large rather than small coronary arteries. After intracoronary infusion in group 3 (n = 6), however, most (94%) of the increase in resistance during vasopressin administration was explained by an increase of resistance in small coronary arteries. In group 4 (n = 9), vasopressin decreased coronary blood flow by 50% and decreased local shortening by 90% at a time when systemic hemodynamics were unchanged. Coronary constriction induced by vasopressin, or the recovery from it, also was not altered by cyclooxygenase blockade. CONCLUSIONS: Thus, vasopressin produces myocardial ischemia by constricting small, nondiseased coronary arteries severely enough to overcome the competition from normal coronary regulation, and this ischemic event is not mediated by prostaglandin products.
Assuntos
Arginina Vasopressina/farmacologia , Circulação Coronária/efeitos dos fármacos , Doença das Coronárias/induzido quimicamente , Vasoconstrição , Animais , Doença das Coronárias/metabolismo , Inibidores de Ciclo-Oxigenase , Cães , Feminino , Hemodinâmica/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Masculino , Miocárdio/metabolismo , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
It remains unknown whether the actions of verapamil to depress and nifedipine to enhance contractile function of ischemic myocardium influence the degree of myocardial ischemic injury. Thus, we measured intramyocardial pH using fiberoptic pH probes in 43 anesthetized open-chest dogs pretreated for 30 min with verapamil, or nifedipine in doses that decreased aortic pressure 10 to 15 mm Hg before ligation of the left anterior descending coronary artery for 15 min. Drugs were continued during the 15-min ischemic period until the animals were euthanized without reperfusion: verapamil, 10-20 micrograms/kg/min and nifedipine, 2 to 4 micrograms/kg/min i.v. Verapamil-treated dogs showed higher pH of ischemic subendocardium after 15 min ischemia (6.75 +/- 0.07) than did the nifedipine (6.48 +/- 0.04) or placebo (6.43 +/- 0.05) groups, even if the animals were paced (6.71 +/- 0.11) to prevent the negative chronotropic effect of verapamil (P less than 0.01). Neither verapamil nor nifedipine changed collateral myocardial blood flow from 0.10 +/- 0.02 in the subendocardium and 0.17 +/- 0.03 ml/min/g in the subepicardium. Left ventricular function estimated by left ventricular dp/dt was depressed 15% by verapamil and enhanced 26% by nifedipine. Thus, verapamil, but not nifedipine, relieves acidosis of ischemic myocardium after acute coronary occlusion in doses that sustain a 10 to 15 mm Hg decrease in aortic pressure. Nifedipine, in doses that produced the same 10 to 15 mm Hg decrease in mean aortic pressure, did not increase intramyocardial pH, as it enhanced contractile function, estimated by left ventricular dp/dt.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Doença das Coronárias/metabolismo , Miocárdio/metabolismo , Nifedipino/farmacologia , Verapamil/farmacologia , Animais , Circulação Coronária/efeitos dos fármacos , Doença das Coronárias/tratamento farmacológico , Cães , Hemodinâmica/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Contração Miocárdica/efeitos dos fármacos , Nifedipino/uso terapêuticoRESUMO
The subendocardium is more susceptible to ischemia than the subepicardium. Studies during critical coronary stenosis have demonstrated subendocardial hypoperfusion relative to the subepicardium and transmural gradients in certain tissue metabolites. Although ischemia causes acidosis, the existence of a transmural pH gradient has never been demonstrated or quantitated. Thus we reduced coronary blood flow to 20 +/- 5% of normal in eight open chest anesthetized (morphine sulfate and pentobarbital) dogs and to 45 +/- 5% in two dogs. We implanted specially designed miniature fiber-optic pH probes in normal and ischemic subendocardium (depth 5.5-8 mm) and subepicardium (depth 3-4 mm). Separate experiments validated use of the fiber-optic pH probe system to measure tissue pH. Although both probes were located in the ischemic zone, there was a large transmural gradient, i.e., from normal pH values (7.36) in the subepicardium to severely acidotic (pH 6.94) 2 mm deeper in the subendocardium. This marked difference in pH between nearby transmural layers may have important implications regarding arrhythmogenesis in the setting of acute myocardial ischemia.