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The porphyrin handbook - Kadish K.M.

Kadish K.M. The porphyrin handbook - Academic press, 2000. - 368 p.
Download (direct link): kadishsmishgulilard2000.djvu
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unventilated catheter tip. The sensor has to be tested under different
experimental conditions to ensure that the sensor did not generate an
analytical signal when subjected to conditions of fluid pressure,
mechanical deformation of the sensor tip, or intrinsic electrical
activity within the heart.
To demonstrate that the sensor does not respond with and to electrical
signal changes in pressure, recordings can be made in an electrolyte-
filled sealed chamber, within which pressure was rapidly altered. As can
be seen in Figure 17, alterations in pressure have no measurable effect
on the amperometric current generated by the sensor, which was immersed
in the confined electrolyte solution. In order to estimate potential
piezoelectric electrical interference due to mechanical deformation of
the sensor tip, a micromanipulator can be used to deform the sensor tip
at a physiologically relevant frequency (1-3 Hz). This usually generates
small electrical noises, six to ten times smaller
250
Malinski
time, ms
Figure 18. Nitric oxide signal and ECC signal recorded simultaneously in
the beating heart (rabbit).
than the signal recorded by the sensor at a low (20-50 nM) concentration
of NO.
To eliminate the possibility that the sensor might respond to the
electrical current generated within the extensive cardiac conduction
system or within the depolarizing myocardium, the sensor can be used as
the exploring electrode connected to a standard ECG. As is apparent from
Figure 17, the porphyrinic sensor, when used in this manner, is barely
able to detect an electrical signal. In these observations of the
sensor's analytic response to potential piezoelectric or in vivo
electrical current interferants, the measured peak of NO was at least 30
to 50 times larger and temporally shifted from the conservatively
estimated background noises.
An anesthetized rabbit was used to measure local fluctuations in NO
concentration in the apical left ventricular endocardium. Rapid changes
in cardiac NO concentration related to the cardiac cycle were observed
(Figure 18). In the rabbit heart (endocardium) each cardiac cycle (period
about 320 ms) begins and ends with an intercycle NO concentration of 0.60
. During early systole, NO concentration reaches a basal of 0.62
followed by a slow increase (20 nM ms-1) to a semiplateau. Early
diastolic filling is accompanied by a brisk of NO with a peak diastolic
2.7 that is attained at 240 ms into the cardiac cycle. After this
peak, there is a sharp decay of the intercycle NO concentration. The NO
signal recorded by the sensor disappears when monitored at a potential
0.40 V (which is 230 mV below the peak potential of NO oxidation),
clearly indicating that the signal measured at
0.63 V is due to NO, not mechanical noises, which are applied independent
of potential. To demonstrate the relationship between the ECG signal and
instantaneous NO concentration, simultaneous recordings of each of these
can be performed (Figure 18).
NO is released in pulsatile fashion from the beating heart and its
synthesis is directly related to ventricular loading conditions in vivo
(Figure 18). Direct measurements of NO
with a porphyrinic sensor in beating heart may help to explain certain
aspects of the beat-to-beat regulation of cardiac performance and also
provide insight into the porphyrinic pathophysiology of diseases
associated with increased myocardial distention, such as valvular heart
disease or heart failure.80 Cells within the heart are subjected to
tremendous mechanical deformation during filling and beating. NO affects
mechanical properties of cardiac myocytes via increasing cGMP to
facilitate relaxation and to mediate an acetylcholine-stimulated decrease
in contractility. Amperometric detection with a porphyrinic sensor is the
only analytical method currently available to measure NO concentration in
the beating heart with sufficient time resolution and sensitivity.
9. Measurements of Nitric Oxide in Human Beings
Porphyrinic catheter-protected sensors can be sterilized with ethylene
oxide and used for NO measurement in humans.75 For measurements of NO in
veins or arteries, an intervenous catheter is used. Two cannulae are
inserted into a vein. A 24 G catheter is inserted retrogradely and a 23 G
butterfly needle is positioned anterogradely with its tip 10-15 mm from
the end of the catheter. The catheter is flushed with
0.5 ml heparin (5000 U/ml) and a nitric oxide sensor is mounted on a 24-G
needle and is placed so its tip protruded
1-2 mm beyond the end of the catheter. A platinum-wire counter electrode
and silver/silverchloride reference electrode can be placed on the skin
adjacent to the vein and covered with conductive gel. Heparin solution
physiological saline or drugs can be infused continuously through the
butterfly needle. Infusion of acetylcholine causes a dose-dependent NO
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