The arterioles of the cat sartorius muscle dilate when arterial pressure is reduced. It has been suggested that this dilation is due to a decrease in blood flow which in turn decreases oxygen delivery and increases tissue production of vasodilator substances. The latter diffuse into the vicinity of the arterioles and cause vascular relaxation. This vascular dilation acts to maintain blood flow through the tissue near the control level at a time when perfusion pressure is reduced. This phenomenon, called autoregulation of blood flow, has been observed in most organs of the body. In the following experiments, we attempted to test the hypothesis that a fall in the oxygen level of the tissue is responsible for blood flow autoregulation. We did this by studying the response of cat sartorius arterioles to arterial pressure reduction under conditions where the muscle was supplied with oxygen from the environment in addition to that normally supplied by the blood. Tissue PO₂ was altered by placing the isolated, auto-perfused cat sartorius muscle in contact with silicone fluid equilibrated with a 0% to 20% oxygen gas mixture. As oxygen tension in the bathing fluid was increased, the preponderant response was a decrease in arteriolar diameter, blood velocity and arteriolar volume flow. To illustrate, 8% of the arterioles constricted by an average of 10% and 18% when the muscle was exposed to oxygen tensions of 66 and 132 mmHg, respectively. When blood flow autoregulation was investigated, it was found that elevated oxygen tension in the bathing fluid abolished any significant arteriolar dilation or flow autoregulation in the majority of arterioles studied. In addition, the elevated oxygen environment caused complete cessation of blood flow in many of the smaller arterioles (< 15μ in diameter). The results of this study strongly suggest that the O₂ level of the tissue is an important determinant in local blood flow regulation.

Diazoxide, a non-diuretic benzothiadiazlne antihypertensive agent, is thought to act directly upon the vascular smooth muscle of the resistance vessels to exert its therapeutic effects in hypertension. Diazoxide may exert its antihypertensive action by antagonizing calcium in vascular smooth muscle. Wohl et al. (1967 and 1968) have suggested such an interaction based on experiments conducted with isolated rabbit aortae. The present experiments were designed to investigate the possible cellular locus of the postulated interaction of diazoxide with calcium using the isolated anterior mesenteric vein of the rabbit as a model of vascular smooth muscle. This vein is spontaneously motile and possesses characteristics similar to those observed for vessels of the microcirculation. Diazoxide at 10ˉ⁴ M inhibited spontaneous motility and its associated membrane electrical activity, and caused hyperpolarization in rabbit anterior mesenteric veins examined with a sucrose gap apparatus. Diazoxide also inhibited spontaneous electrical and contractile activity in guinea-pig taenia coli and in estrogen dominated rabbit uterus. In all these tissues, calcium is believed to play an important role in spontaneous electrical membrane activity. Diazoxide failed to affect contractility, rate of spontaneous contractions, or action potential configurations in isolated rabbit heart, even though the action potential in heart tissues possesses a definite calcium current component. Diazoxide reduced contractions induced in the mesenteric vein by electrical stimulation of the smooth muscle itself or by excitation of the nerve endings within the vein. Various drugs were chosen for their ability to contract the mesenteric vein in different ways. Noradrenaline contracts vascular smooth muscle even when the tissue Is depolarized with ouabain Diazoxide failed to inhibit noradrenaline contractions in the depolarized vein, but showed the characteristics of a competitive inhibitor of noradrenaline in normally polarized veins. Diazoxide was also capable of inhibiting contractions to serotonin and procaine, agents which require membrane polarization to initiate contraction. The inhibitory effect of diazoxide was not observed to be modified in solutions containing high concentrations of calcium. Diazoxide was tested upon the contractile responses to calcium In veins depolarized in K⁺ Ringer solution. Examination of the resultant dose response curves showed that diazoxide inhibited calcium contractions ln a reversible, non surmountable manner. Hydrochlorothiazide had no effect upon calcium induced contractions. Diazoxide antagonizes drug induced contractions only if a polarized membrane is present. Calcium Induced contractions in depolarizing solutions were inhibited in an apparently Insurmountable manner, while drug responses in polarizing solutions were inhibited by diazoxide in a surmountable manner. In addition, action potentials from rabbit heart were unchanged whereas, the apparently calcium spike mediated electrical activity of certain smooth muscles is inhibited. It is concluded that diazoxide affects the membrane of vascular smooth muscle to reduce excitability of the tissue to drugs or electrical stimuli. It is possible that cell membrane bound calcium could be the locus of action of diazoxide and that this agent modifies membrane calcium to cause increased membrane stability. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Na reconstrução mamária com microcirurgia, a qualidade dos vasos, a proximidade com a região torácica e a anatomia constante são fatores relevantes na escolha do pedículo receptor. Apesar da grande aplicação clínica, os vasos toracodorsais e torácicos internos apresentam restrições como a imprevisibilidade da qualidade nas reconstruções tardias, as alterações do contorno do tórax e a inviabilidade de uma eventual revascularização futura do miocárdio. Com o desenvolvimento dos retalhos vascularizados por vasos perfurantes e o maior treinamento dos cirurgiões, novas alternativas de pedículos foram desenvolvidas. A preservação da cartilagem costal e dos vasos torácicos internos, bem como a maior exposição do campo operatório são mencionados como vantagens do emprego dos vasos perfurantes do músculo peitoral maior como receptor. Apesar da anatomia dos vasos perfurantes ter sido previamente estudada, são imprecisas as informações sobre sua origem e distribuição no tórax. Ademais, são escassos os dados relacionados à sua incidência e utilização nas reconstruções imediatas e tardias. Na presente investigação foram incluídos dois estudos: anatômico e clínico. No estudo anatômico avaliou-se a origem, distribuição e dimensões dos vasos perfurantes em 24 cadáveres frescos (48 regiões torácicas), por técnica de coloração e posterior dissecção. No estudo clínico analisou-se, 69 pacientes (77 reconstruções mamárias), sendo 46 imediatas e 31 tardias. Constatou-se no estudo anatômico 2,7 vasos perfurantes por região torácica, destes, 93% apresentaram pequeno e médio calibre e concentração preferencial no segundo espaço intercostal. Os vasos e o pedículo perfurante revelaram comprimento médio de 2,4 cm (1,0 a 3,2 cm) e 3,6 cm (2,1 a 4,5 cm), respectivamente. No estudo clínico, não foram observadas diferenças entre as pacientes submetidas à reconstrução imediata e tardia, quanto a idade (p=0,599), IMC (p=0,498), lateralidade da mama (p=0,671), hipertensão arterial sistêmica (p=0,732), diabetes (p>0,999) e tabagismo (0,828). Todavia, 61,3% das pacientes submetidas à reconstrução tardia relataram radioterapia previamente à cirurgia (p<0,001). Nas reconstruções imediatas, em 93,5% dos casos os vasos perfurantes estavam presentes e, em 37,2%, foi possível realizar as anastomoses. Entre as causas de insucesso das anastomoses destacaram-se a lesão vascular durante a mastectomia (48,8%) e a desproporção de calibre dos vasos (13,9%). Nas reconstruções tardias, em 12,9% dos casos, os vasos perfurantes estavam presentes e em nenhum caso foi possível realizar as anastomoses. A incompatibilidade de calibre dos vasos e a má qualidade da estrutura vascular foram as razões para não os empregar como pedículo receptor. Não foram observadas diferenças estatísticas quanto à incidência de complicações gerais (p=0,548), perda parcial do retalho (p=0,494), perda total do retalho (p=0,644) e necrose da pele remanescente da mastectomia (p=0,193) nas pacientes submetidas à reconstrução com pedículo receptor perfurante e com os demais pedículos receptores. Os resultados permitiram-nos concluir que a maior concentração de vasos perfurantes no segundo espaço intercostal e a distância entre 0,5 e 3 cm do esterno constituem parâmetros anatômicos importantes no planejamento da técnica. É recomendável que nas reconstruções imediatas se faça o planejamento prévio com o mastologista com intuito de preservar os vasos perfurantes, enquanto que nas reconstruções tardias, a presença de cirurgia prévia e da radioterapia podem se relacionar à menor reprodutibilidade da técnica / In breast reconstruction with microsurgery, the proper selection of the recipient pedicle is a significant factor for success. The compatibility of caliber and the uniform anatomy are the chief relevant factors in the choice of recipient vessels. Regardless of their broad clinical application, the thoracodorsal and internal thoracic vessels demonstrate limitations such as the unpredictable quality of late reconstructions, the changes in thoracic contour and the impairment for future coronary bypass. The progress of microsurgical technique and the development of perforator flaps has led to new recipient pedicle alternatives. Thus, sparing of the costal cartilages and the internal thoracic vessels as well as the wide surgical exposure are the main advantages of using the pectoralis major perforator vessels as recipient pedicles. Although the anatomy of the perforator vessels has been previously studied, the data about their origin and distribution is inexact. In addition, the data concerning their incidence and quality of immediate and late reconstructions are not available. In the present investigation, an anatomical and clinical study were performed. In the anatomical study, the origin, distribution and size of perforator vessels were evaluated in 24 fresh cadavers (48 thoracic regions) by staining technique and posterior dissection. The clinical study analyzed 69 patients (77 reconstructions), 46 immediate and 31 late reconstructions. The anatomic study observed 2.7 perforator vessels per thoracic region, with 93% presenting small and medium caliber and major concentration in the second intercostal space. The vessels and the perforator pedicles demonstrated an average length of 2.4 cm (1.0 to 3.2 cm) and 3.6 cm (2.1 to 4.5 cm) respectively. In the clinical study, no differences were observed between the immediate and late reconstructions regarding age (p=0.599), BMI (p=0.498), breast side (p=0.671), hypertension (p=0.732), diabetes (p>0.999) and smoking (0.828). Nevertheless, 61.3% of patients submitted to late reconstruction had radiotherapy prior to breast reconstruction (p<0.001). The perforator vessels were observed in 93.5% of the immediate reconstructions and vascular anastomosis was performed in 37.2%. Vascular injury during mastectomy (48.8%) and caliber compatibility (13.9%) were observed as the main causes of failure anastomosis. In late reconstructions, the perforator vessels were present in 12.9% and the anastomosis was impossible in all cases due to caliber differences and vascular quality. No statistical differences were observed regarding the incidence of general complications (p=0.548), partial loss (p=0.494), total loss (p=0.644) and mastectomy flap necrosis (p=0.193) in patients submitted to reconstruction with perforator vessels and the other recipient pedicles. The present study enabled us to conclude that the major concentration of perforator vessels in the second intercostal space and the distance between 0.5 and 3 cm from the sternal region represent an important anatomic parameter. In immediate reconstructions, a preoperative planning between the general and plastic surgeon is fundamental to preserve the main perforator vessels during the mastectomy. In late reconstructions the procedure was not demonstrable and some factors may be involved such as previous surgery and radiation therapy

Na reconstrução mamária com microcirurgia, a qualidade dos vasos, a proximidade com a região torácica e a anatomia constante são fatores relevantes na escolha do pedículo receptor. Apesar da grande aplicação clínica, os vasos toracodorsais e torácicos internos apresentam restrições como a imprevisibilidade da qualidade nas reconstruções tardias, as alterações do contorno do tórax e a inviabilidade de uma eventual revascularização futura do miocárdio. Com o desenvolvimento dos retalhos vascularizados por vasos perfurantes e o maior treinamento dos cirurgiões, novas alternativas de pedículos foram desenvolvidas. A preservação da cartilagem costal e dos vasos torácicos internos, bem como a maior exposição do campo operatório são mencionados como vantagens do emprego dos vasos perfurantes do músculo peitoral maior como receptor. Apesar da anatomia dos vasos perfurantes ter sido previamente estudada, são imprecisas as informações sobre sua origem e distribuição no tórax. Ademais, são escassos os dados relacionados à sua incidência e utilização nas reconstruções imediatas e tardias. Na presente investigação foram incluídos dois estudos: anatômico e clínico. No estudo anatômico avaliou-se a origem, distribuição e dimensões dos vasos perfurantes em 24 cadáveres frescos (48 regiões torácicas), por técnica de coloração e posterior dissecção. No estudo clínico analisou-se, 69 pacientes (77 reconstruções mamárias), sendo 46 imediatas e 31 tardias. Constatou-se no estudo anatômico 2,7 vasos perfurantes por região torácica, destes, 93% apresentaram pequeno e médio calibre e concentração preferencial no segundo espaço intercostal. Os vasos e o pedículo perfurante revelaram comprimento médio de 2,4 cm (1,0 a 3,2 cm) e 3,6 cm (2,1 a 4,5 cm), respectivamente. No estudo clínico, não foram observadas diferenças entre as pacientes submetidas à reconstrução imediata e tardia, quanto a idade (p=0,599), IMC (p=0,498), lateralidade da mama (p=0,671), hipertensão arterial sistêmica (p=0,732), diabetes (p>0,999) e tabagismo (0,828). Todavia, 61,3% das pacientes submetidas à reconstrução tardia relataram radioterapia previamente à cirurgia (p<0,001). Nas reconstruções imediatas, em 93,5% dos casos os vasos perfurantes estavam presentes e, em 37,2%, foi possível realizar as anastomoses. Entre as causas de insucesso das anastomoses destacaram-se a lesão vascular durante a mastectomia (48,8%) e a desproporção de calibre dos vasos (13,9%). Nas reconstruções tardias, em 12,9% dos casos, os vasos perfurantes estavam presentes e em nenhum caso foi possível realizar as anastomoses. A incompatibilidade de calibre dos vasos e a má qualidade da estrutura vascular foram as razões para não os empregar como pedículo receptor. Não foram observadas diferenças estatísticas quanto à incidência de complicações gerais (p=0,548), perda parcial do retalho (p=0,494), perda total do retalho (p=0,644) e necrose da pele remanescente da mastectomia (p=0,193) nas pacientes submetidas à reconstrução com pedículo receptor perfurante e com os demais pedículos receptores. Os resultados permitiram-nos concluir que a maior concentração de vasos perfurantes no segundo espaço intercostal e a distância entre 0,5 e 3 cm do esterno constituem parâmetros anatômicos importantes no planejamento da técnica. É recomendável que nas reconstruções imediatas se faça o planejamento prévio com o mastologista com intuito de preservar os vasos perfurantes, enquanto que nas reconstruções tardias, a presença de cirurgia prévia e da radioterapia podem se relacionar à menor reprodutibilidade da técnica / In breast reconstruction with microsurgery, the proper selection of the recipient pedicle is a significant factor for success. The compatibility of caliber and the uniform anatomy are the chief relevant factors in the choice of recipient vessels. Regardless of their broad clinical application, the thoracodorsal and internal thoracic vessels demonstrate limitations such as the unpredictable quality of late reconstructions, the changes in thoracic contour and the impairment for future coronary bypass. The progress of microsurgical technique and the development of perforator flaps has led to new recipient pedicle alternatives. Thus, sparing of the costal cartilages and the internal thoracic vessels as well as the wide surgical exposure are the main advantages of using the pectoralis major perforator vessels as recipient pedicles. Although the anatomy of the perforator vessels has been previously studied, the data about their origin and distribution is inexact. In addition, the data concerning their incidence and quality of immediate and late reconstructions are not available. In the present investigation, an anatomical and clinical study were performed. In the anatomical study, the origin, distribution and size of perforator vessels were evaluated in 24 fresh cadavers (48 thoracic regions) by staining technique and posterior dissection. The clinical study analyzed 69 patients (77 reconstructions), 46 immediate and 31 late reconstructions. The anatomic study observed 2.7 perforator vessels per thoracic region, with 93% presenting small and medium caliber and major concentration in the second intercostal space. The vessels and the perforator pedicles demonstrated an average length of 2.4 cm (1.0 to 3.2 cm) and 3.6 cm (2.1 to 4.5 cm) respectively. In the clinical study, no differences were observed between the immediate and late reconstructions regarding age (p=0.599), BMI (p=0.498), breast side (p=0.671), hypertension (p=0.732), diabetes (p>0.999) and smoking (0.828). Nevertheless, 61.3% of patients submitted to late reconstruction had radiotherapy prior to breast reconstruction (p<0.001). The perforator vessels were observed in 93.5% of the immediate reconstructions and vascular anastomosis was performed in 37.2%. Vascular injury during mastectomy (48.8%) and caliber compatibility (13.9%) were observed as the main causes of failure anastomosis. In late reconstructions, the perforator vessels were present in 12.9% and the anastomosis was impossible in all cases due to caliber differences and vascular quality. No statistical differences were observed regarding the incidence of general complications (p=0.548), partial loss (p=0.494), total loss (p=0.644) and mastectomy flap necrosis (p=0.193) in patients submitted to reconstruction with perforator vessels and the other recipient pedicles. The present study enabled us to conclude that the major concentration of perforator vessels in the second intercostal space and the distance between 0.5 and 3 cm from the sternal region represent an important anatomic parameter. In immediate reconstructions, a preoperative planning between the general and plastic surgeon is fundamental to preserve the main perforator vessels during the mastectomy. In late reconstructions the procedure was not demonstrable and some factors may be involved such as previous surgery and radiation therapy